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大髙章

徳島大学

プロフィール
教育活動
研究活動
社会活動
リサーチマップ・
Jグローバル
KAKEN
注目研究

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2024年12月19日更新

職名: 教授
電話: 研究者総覧に該当データはありませんでした。
電子メール: aotaka@tokushima-u.ac.jp
学歴: 1989/3: 京都大学大学院薬学研究科博士後期課程製薬化学専攻修了
学位: 薬学博士 (京都大学) (1989年3月)
職歴・経歴: 〜: 徳島大学教授, 大学院ヘルスバイオサイエンス研究部 (-2015.3.)
2015/4: 徳島大学教授, 大学院医歯薬学研究部

専門分野・研究分野: 生物有機化学
有機合成化学
ペプチド・タンパク質化学
ケミカルバイオロジー

研究者総覧で最新データを確認する

2024年12月19日更新

専門分野・研究分野: 生物有機化学
有機合成化学
ペプチド・タンパク質化学
ケミカルバイオロジー
担当経験のある授業科目: ケミカルバイオロジー共通演習 (大学院)
創薬研究実践特論 (大学院)
創薬科学演習 (大学院)
創薬科学特論 (大学院)
医薬品化学 (学部)
基礎化学Ⅲ・薬の科学 (共通教育)
専攻公開ゼミナール (大学院)
有機化学5(生体分子) (学部)
有機化学実習 (学部)
薬と社会の探訪 (学部)
薬科学演習1 (大学院)
薬科学特別研究 (大学院)
指導経験: 11人 (修士), 5人 (博士)

研究者総覧で最新データを確認する

2024年12月19日更新

専門分野・研究分野: 生物有機化学
有機合成化学
ペプチド・タンパク質化学
ケミカルバイオロジー

研究テーマ: 創薬基盤確立に向けた効率的なタンパク質化学合成法の開拓

著書

大髙章 :
「4章『失敗の言語化』が拓いたリバイバル研究」ドラマチック有機合成化学感動の瞬間100 (有機合成化学協会編),
株式会社化学同人, 2023年7月. 大髙章 :
「1章現場で必要な臨床医薬品化学とは，6章糖尿病とその治療薬」現場で役に立つ!臨床医薬品化学 (臨床医薬品化学研究会編),
株式会社化学同人, 2021年4月. 大髙章, 重永章 :
「第I編ペプチド合成，第二章ペプチドの液相合成」医療・診断をささえるペプチド科学―再生医療・DDS・診断への応用―(平野義明監修),
株式会社シーエムシー出版, 2017年10月. 重永章, 山本純, 大髙章 :
実験医学増刊号驚愕の代謝システムメタボロームの階層から解き明かす疾患研究の新たなステージ「生物活性小分子の結合パートナータンパク質を知りたい -リンカー分子を用いたタンパク質精製法-」,
株式会社羊土社, 2014年9月. 大髙章 :
生体有機化学第12章生理活性ペプチドホルモン,
株式会社東京化学同人, 2012年10月. 重永章, 山本純, 大髙章 :
遺伝子医学MOOK 21号最新ペプチド合成技術とその創薬研究への応用, 刺激応答型アミノ酸の開発と生命科学分野への応用,
メディカルドゥ, 2012年4月. 大髙章, 重永章 :
機能性タンパク質・ペプチドの生体利用，第10章最近のペプチド・タンパク質の化学合成について,
株式会社建帛社, 2010年5月. 大髙章 :
新しい薬をどう創るか, --- 創薬研究の最前線 ---,
株式会社講談社, 東京, 2007年4月. 大髙章 :
タンパク質化学第11巻, --- ホルモン系タンパク質およびポリアミン ---,
株式会社廣川書店, 東京, 1997年. 藤井信孝, 大髙章 :
新生化学実験講座1 タンパク質6, --- 合成および発現 ---,
株式会社東京化学同人, 東京, 1992年6月. 木曽良明, 大髙章 :
続医薬品の開発第14巻, --- ペプチド合成 ---,
株式会社廣川書店, 東京, 1991年.

論文

Tsuji Takashi, Hayato INAZUKI, Kobayashi Daishiro, Hayashi JUNYA, Masaya Denda and Akira Otaka :
Cysteinylprolyl ester-mediated drug release from a lipid-drug conjugate,
Bioorganic & Medicinal Chemistry Letters, Vol.109, 129850, 2024.

(要約): For small-molecule drugs, lipidation via a cleavable linkage can extend half-life in circulation through interaction with albumin. Here we modified the cysteinylprolyl ester (CPE) system used in peptide thioester synthesis, which normally requires basic conditions, for use as an self-immolative linker and release device for a lipid-gemcitabine conjugate. To improve release under physiological conditions for medical application, a methyl group at the α-position of cysteine on the CPE unit was incorporated in anticipation of the Thorpe-Ingold effect. As a result, Ac-Gly-(α-Me)Cys(SH)-Pro-gemcitabine 11 drastically promoted the release of gemcitabine in comparison with Ac-Gly-Cys(SH)-Pro-gemcitabine 10. Furthermore, in the presence of bovine serum albumin and/or 2-mercaptoethanesulfonic acid, the gentle and continuous release of gemcitabine from the lipid-gemcitabine conjugate 16 was achieved. In addition to gemcitabine, this method could allow high clearance drugs, including nucleic acid and prostacyclin derivatives, to maintain their biological activity long enough to become effective.
(キーワード): Gemcitabine / Deoxycytidine / Lipids / Esters / Drug Liberation / Cysteine / Humans / Molecular Structure / Serum Albumin, Bovine / Animals
(徳島大学機関リポジトリ): ● Metadata: 119452
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bmcl.2024.129850
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38879090; ● Summary page in Scopus @ Elsevier: 2-s2.0-85196376333

(徳島大学機関リポジトリ: 119452, DOI: 10.1016/j.bmcl.2024.129850, PubMed: 38879090, Elsevier: Scopus) Daishiro Kobayashi, Masaya Denda, Junya Hayashi, Kohta Hidaka, Yutaka Kohmura, Takaaki Tsunematsu, Kohei Nishino, Harunori Yoshikawa, OHKAWACHI Kento, Kiyomi Nigorikawa, Tetsuro Yoshimaru, Naozumi Ishimaru, Wataru Nomura, Toyomasa Katagiri, Hidetaka Kosako and Akira Otaka :
Sulfoxide-Mediated Cys-Trp-Selective Bioconjugation that Enables Protein Labeling and Peptide Heterodimerization,
ChemistryEurope, Vol.2, No.3-4, 2024.

(出版サイトへのリンク): ● Publication site (DOI): 10.1002/ceur.202400014
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1002/ceur.202400014

(DOI: 10.1002/ceur.202400014) Junya Hayashi, Daishiro Kobayashi, Masaya Denda and Akira Otaka :
Late-stage formation of a sactionine linkage enabled by Lossen rearrangement of glycyl hydroxamic acid,
Organic Letters, Vol.26, No.24, 5167-5171, 2024.

(要約): Late-stage formation of a sactionine thioether bond connecting a Gly α-carbon and Cys thiol was achieved by Lossen rearrangement of a glycyl hydroxamic acid (GlyHA) residue in a peptide. Lossen rearrangement allowed conversion of GlyHA within a peptide to an -acyl iminium equivalent, which subsequently reacted with -acetamidomethyl Cys (Cys(Acm)) in TFA in the presence of guanidine hydrochloride (Gn·HCl) to yield the desired thioether linkage in the final stage.
(徳島大学機関リポジトリ): ● Metadata: 119421
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.orglett.4c01685
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38848136; ● Summary page in Scopus @ Elsevier: 2-s2.0-85195570491

(徳島大学機関リポジトリ: 119421, DOI: 10.1021/acs.orglett.4c01685, PubMed: 38848136, Elsevier: Scopus) Junya Hayashi, Daishiro Kobayashi, Chizuru Namikawa, Masaya Denda and Akira Otaka :
Synthesis of N-Glyoxylyl Peptides Enabled by a Lossen Rearrangement-Induced Intramolecular Redox Reaction of N-Terminal Glycyl Hydroxamic Acid,
Organic Letters, Vol.26, No.20, 4246-4250, 2024.

(要約): An oxidant-free approach to the synthesis of -glyoxylyl peptides has been developed that utilizes the Lossen rearrangement of the N-terminal glycyl hydroxamic acid residue. The synthesis proceeds via an intramolecular redox mechanism to yield the glyoxylyl peptides, which are then subjected to various peptide cyclization procedures. The reaction scheme is suitable for oxidation-sensitive moieties including amino acids.
(徳島大学機関リポジトリ): ● Metadata: 119346
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.orglett.4c01126
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38738629; ● Search Scopus @ Elsevier (PMID): 38738629; ● Search Scopus @ Elsevier (DOI): 10.1021/acs.orglett.4c01126

(徳島大学機関リポジトリ: 119346, DOI: 10.1021/acs.orglett.4c01126, PubMed: 38738629) Kohta Hidaka, Daishiro Kobayashi, Junya Hayashi, Masaya Denda and Akira Otaka :
Advanced Insulin Synthesis by One-pot/Stepwise Disulfide Bond Formation Enabled by S-Protected Cysteine Sulfoxide,
Chemistry - A European Journal, Vol.30, No.39, e202401003, 2024.

(要約): An advanced insulin synthesis is presented that utilizes one-pot/stepwise disulfide bond formation enabled by acid-activated S-protected cysteine sulfoxides in the presence of chloride anion. S-chlorocysteine generated from cysteine sulfoxides reacts with an S-protected cysteine to afford S-sulfenylsulfonium cation, which then furnishes the disulfide or reversely returns to the starting materials depending on the S-protection employed and the reaction conditions. Use of S-acetamidomethyl cysteine (Cys(Acm)) and its sulfoxide (Cys(Acm)(O)) selectively give the disulfide under weak acid conditions in the presence of MgCl2 even if S-p-methoxybenzyl cysteine (Cys(MBzl)) and its sulfoxide (Cys(MBzl)(O)) are also present. In contrast, the S-MBzl pair yields the disulfide under more acidic conditions in the presence of a chloride anion source. These reaction conditions allowed a one-pot insulin synthesis. Additionally, lipidated insulin was prepared by a one-pot disulfide-bonding/lipidation sequence.
(徳島大学機関リポジトリ): ● Metadata: 119333
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/chem.202401003
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38683139; ● Search Scopus @ Elsevier (PMID): 38683139; ● Search Scopus @ Elsevier (DOI): 10.1002/chem.202401003

(徳島大学機関リポジトリ: 119333, DOI: 10.1002/chem.202401003, PubMed: 38683139) Rin Miyajima, Kosuke Tanegashima, Naoto Naruse, Masaya Denda, Takahiro Hara and Akira Otaka :
Identification of Low-Density Lipoprotein Receptor-Related Protein 1 as a CXCL14 Receptor Using Chemically Synthesized Tetrafunctional Probes,
ACS Chemical Biology, Vol.19, No.2, 551-562, 2024.

(要約): CXCL14 is a primordial CXC-type chemokine that transports CpG oligodeoxynucleotides (ODN) into endosomes and lysosomes in dendritic cells, thereby leading to the activation of the Toll-like receptor 9 (TLR9)-mediated innate immune system. However, the underlying molecular mechanism by which the CXCL14-CpG ODN complex enters cells remains elusive. Herein, we describe the chemical synthesis of CXCL14-derived photoaffinity probes and their application to the identification of target receptors for CXCL14 using quantitative proteomics. By utilizing native chemical ligation and maleimide-thiol coupling chemistry, we synthesized site-specifically modified CXCL14-based photoaffinity probes that contain photoreactive 2-aryl-5-carboxytetrazole (ACT) and a hydrazine-labile cleavable linker. CXCL14-based probes were found to be capable of binding CpG ODN to immune cells, whose bioactivities were comparable to native CXCL14. Application of CXCL14-derived probes to quantitative proteomic experiments enabled the identification of dozens of target receptor candidates for CXCL14 in mouse macrophage-derived RAW264.7 cells, and we discovered that low-density lipoprotein receptor-related protein 1 (LRP1) is a novel receptor for CXCL14 by competitive proteome profiling. We further showed that disruption of LRP1 affected the incorporation of the CXCL14-CpG ODN complex in the cells. Overall, this report highlights the power of synthetic CXCL14-derived photoaffinity probes combined with chemical proteomics to discover previously unidentified receptors for CXCL14, which could promote an understanding of the molecular functions of CXCL14 and the elaborate machinery of innate immune systems.
(キーワード): Animals / Mice / Low Density Lipoprotein Receptor-Related Protein-1 / Proteomics / Oligodeoxyribonucleotides / Lipoproteins, LDL / Chemokines, CXC
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acschembio.3c00717
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38289037; ● Search Scopus @ Elsevier (PMID): 38289037; ● Search Scopus @ Elsevier (DOI): 10.1021/acschembio.3c00717

(DOI: 10.1021/acschembio.3c00717, PubMed: 38289037) Masaki Imanishi, Takahisa Inoue, Keijo Fukushima, Ryosuke Yamashita, Ryo Nakayama, Masataka Nojima, Kosuke Kondo, Yoshiki Gomi, Honoka Tsunematsu, Kohei Goto, Licht Miyamoto, Masafumi Funamoto, Masaya Denda, Keisuke Ishizawa, Akira Otaka, Hiromichi Fujino, Yasumasa Ikeda and Koichiro Tsuchiya :
CA9 and PRELID2; hypoxia-responsive potential therapeutic targets for pancreatic ductal adenocarcinoma as per bioinformatics analyses.,
Journal of Pharmacological Sciences, Vol.153, No.4, 232-242, 2023.

(要約): A strong hypoxic environment has been observed in pancreatic ductal adenocarcinoma (PDAC) cells, which contributes to drug resistance, tumor progression, and metastasis. Therefore, we performed bioinformatics analyses to investigate potential targets for the treatment of PDAC. To identify potential genes as effective PDAC treatment targets, we selected all genes whose expression level was related to worse overall survival (OS) in The Cancer Genome Atlas (TCGA) database and selected only the genes that matched with the genes upregulated due to hypoxia in pancreatic cancer cells in the dataset obtained from the Gene Expression Omnibus (GEO) database. Although the extracted 107 hypoxia-responsive genes included the genes that were slightly enriched in angiogenic factors, TCGA data analysis revealed that the expression level of endothelial cell (EC) markers did not affect OS. Finally, we selected CA9 and PRELID2 as potential targets for PDAC treatment and elucidated that a CA9 inhibitor, U-104, suppressed pancreatic cancer cell growth more effectively than 5-fluorouracil (5-FU) and PRELID2 siRNA treatment suppressed the cell growth stronger than CA9 siRNA treatment. Thus, we elucidated that specific inhibition of PRELID2 as well as CA9, extracted via exhaustive bioinformatic analyses of clinical datasets, could be a more effective strategy for PDAC treatment.
(キーワード): Humans / Carbonic Anhydrase IX / Antigens, Neoplasm / Carcinoma, Pancreatic Ductal / Pancreatic Neoplasms / Hypoxia / RNA, Small Interfering / Computational Biology / Pancreatic Neoplasms
(徳島大学機関リポジトリ): ● Metadata: 119176
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.jphs.2023.10.003
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37973221; ● CiNii @ 国立情報学研究所 (CRID): 1872553967456110848; ● Search Scopus @ Elsevier (PMID): 37973221; ● Search Scopus @ Elsevier (DOI): 10.1016/j.jphs.2023.10.003

(徳島大学機関リポジトリ: 119176, DOI: 10.1016/j.jphs.2023.10.003, PubMed: 37973221, CiNii: 1872553967456110848) Takashi Tsuji, Honoka Tsunematsu, Masaki Imanishi, Masaya Denda, Koichiro Tsuchiya and Akira Otaka :
Enhanced tumor specific drug release by hypoxia sensitive dual-prodrugs based on 2-nitroimidazole,
Bioorganic & Medicinal Chemistry Letters, 129484, 2023.

(要約): Hypoxia in cancer is important in the development of cancer-selective medicines. Here, a novel hypoxia-responsible dual-prodrug is described. We designed and synthesized 2-nitroimidazole derivatives which spontaneously release both a PYG inhibitor and gemcitabine under hypoxic conditions. One such derivative, a prodrug 9 was found to be stable against chemical and enzymatic hydrolysis, and upon chemical reduction of the nitro group on imidazole, successfully releases both drugs. In an in vitro proliferation assay using human pancreatic cells, compound 9 exhibited significant anti-proliferative effects in hypoxia but fewer effects in normoxia. Consequently, prodrug 9 should be useful for cancer treatment due to its improved cancer selectivity and potential to overcome drug resistance.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bmcl.2023.129484
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37716415; ● Search Scopus @ Elsevier (PMID): 37716415; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmcl.2023.129484

(DOI: 10.1016/j.bmcl.2023.129484, PubMed: 37716415) OHKAWACHI Kento, Kaito Anzaki, Daishiro Kobayashi, Ryuji Kyan, Takuma Yasuda, Masaya Denda, Norio Harada, Akira Shigenaga, Nobuya Inagaki and Akira Otaka :
Residue-selective CH sulfenylation enabled by acid-activated S-acetamidomethyl cysteine sulfoxide with application to one-pot stapling and lipidation sequence,
Chemistry - A European Journal, Vol.29, No.26, e202300799, 2023.

(要約): A tyrosine (Tyr)- or tryptophan (Trp)-selective metal-free C-H sulfenylation reaction using an acid-activated S-acetamidomethyl cysteine (Cys) sulfoxide, Cys(Acm)(O), has been achieved. The dually protonated intermediate produced from Cys(Acm)(O) under acidic conditions allows the sulfenylation of Tyr. Significantly, the reaction in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) mainly affords a Cys-Tyr-linked peptide even in the presence of Trp residues. In contrast, a Cys-Trp-linked peptide was selectively obtained from the reaction in the presence of guanidine hydrochloride (Gn ⋅ HCl) under acidic conditions. Established Tyr- and Trp-selective sulfenylation methods were used in the Cys-Tyr stapling and Trp lipidation of glucagon-like peptides 1 in a one-pot/stepwise manner. Investigation of the mechanism showed that orbital- and charge-controlled reactions are responsible for the Trp and Tyr selectivity, respectively.
(キーワード): Cysteine / Peptides / Tyrosine / Sulfoxides / Guanidine
(徳島大学機関リポジトリ): ● Metadata: 118080
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/chem.202300799
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 36922350; ● CiNii @ 国立情報学研究所 (CRID): 1360861705587936000; ● Search Scopus @ Elsevier (PMID): 36922350; ● Search Scopus @ Elsevier (DOI): 10.1002/chem.202300799

(徳島大学機関リポジトリ: 118080, DOI: 10.1002/chem.202300799, PubMed: 36922350, CiNii: 1360861705587936000) Misaki Yamasaki, Yuika Seto, Mizune Ohzono, Michiyasu Nakao, Akira Shigenaga, Akira Otaka, Shigeki Sano and Kentaro Kogure :
Development of a novel tocopheryl ester for suppression of lipid accumulation without cytotoxicity by optimization of dicarboxylic ester moiety,
Biochemistry and Biophysics Reports, Vol.31, 101329, 2022.

(徳島大学機関リポジトリ): ● Metadata: 117361
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrep.2022.101329
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrep.2022.101329

(徳島大学機関リポジトリ: 117361, DOI: 10.1016/j.bbrep.2022.101329) Daishiroh Kobayashi, KURAOKA Eisuke, Junya Hayashi, Takuma Yasuda, Yutaka Kohmura, Masaya Denda, Norio Harada, Nobuya Inagaki and Akira Otaka :
S-Protected cysteine sulfoxide-enabled tryptophan-selective modification with application to peptide lipidation,
ACS Medicinal Chemistry Letters, Vol.13, No.7, 1125-1130, 2022.

(徳島大学機関リポジトリ): ● Metadata: 117175
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acsmedchemlett.2c00161
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1021/acsmedchemlett.2c00161

(徳島大学機関リポジトリ: 117175, DOI: 10.1021/acsmedchemlett.2c00161) Masato Miyake, Mitsuaki Sobajima, Kiyoe Kurahashi, Akira Shigenaga, Masaya Denda, Akira Otaka, Tomohide Saio, Naoki Sakane, Hidetaka Kosako and Seiichi Oyadomari :
Identification of an endoplasmic reticulum proteostasis modulator that enhances insulin production in pancreatic β cells.,
Cell Chemical Biology, Vol.29, No.6, 996-1009.e9, 2022.

(要約): Perturbation of endoplasmic reticulum (ER) proteostasis is associated with impairment of cellular function in diverse diseases, especially the function of pancreatic β cells in type 2 diabetes. Restoration of ER proteostasis by small molecules shows therapeutic promise for type 2 diabetes. Here, using cell-based screening, we report identification of a chemical chaperone-like small molecule, KM04794, that alleviates ER stress. KM04794 prevented protein aggregation and cell death caused by ER stressors and a mutant insulin protein. We also found that this compound increased intracellular and secreted insulin levels in pancreatic β cells. Chemical biology and biochemical approaches revealed that the compound accumulated in the ER and interacted directly with the ER molecular chaperone BiP. Our data show that this corrector of ER proteostasis can enhance insulin storage and pancreatic β cell function.
(キーワード): Diabetes Mellitus, Type 2 / Endoplasmic Reticulum / Endoplasmic Reticulum Stress / Humans / Insulin / Insulin-Secreting Cells / Proteostasis / Unfolded Protein Response
(徳島大学機関リポジトリ): ● Metadata: 116761
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.chembiol.2022.01.002
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35143772; ● Search Scopus @ Elsevier (PMID): 35143772; ● Search Scopus @ Elsevier (DOI): 10.1016/j.chembiol.2022.01.002

(徳島大学機関リポジトリ: 116761, DOI: 10.1016/j.chembiol.2022.01.002, PubMed: 35143772) Daiki Sato, Masaya Denda, Honoka Tsunematsu, Naonobu Tanaka, Isamu Konishi, Chiaki Komiya, Akira Shigenaga and Akira Otaka :
Late-stage macrolactonisation enabled by tandem acyl transfers followed by desulphurisation,
Chemical Communications, Vol.58, No.17, 2918-2921, 2022.

(要約): Intramolecular -acylation of a thiol-installed threonine with a thioester unit, followed by S-O acyl transfer and subsequent desulphurisation, allows the synthesis of lactone peptides. A protocol has been developed enabling the cyclisation of a linear peptide, a reaction which has not been achieved by conventional methods.
(キーワード): Lactones / Molecular Structure / Peptides / Sulfhydryl Compounds / Threonine
(徳島大学機関リポジトリ): ● Metadata: 116717
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/D1CC07248J
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35138311; ● Search Scopus @ Elsevier (PMID): 35138311; ● Search Scopus @ Elsevier (DOI): 10.1039/D1CC07248J

(徳島大学機関リポジトリ: 116717, DOI: 10.1039/D1CC07248J, PubMed: 35138311) Daishiroh Kobayashi, Yutaka Kohmura, Junya Hayashi, Masaya Denda, Koichiro Tsuchiya and Akira Otaka :
Copper (II)-mediated C-H sulphenylation or selenylation of tryptophan enabling macrocyclization of peptides,
Chemical Communications, Vol.57, 10763-10766, 2021.

(徳島大学機関リポジトリ): ● Metadata: 116325
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/D1CC04856B
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34585682; ● Search Scopus @ Elsevier (PMID): 34585682; ● Search Scopus @ Elsevier (DOI): 10.1039/D1CC04856B

(徳島大学機関リポジトリ: 116325, DOI: 10.1039/D1CC04856B, PubMed: 34585682) Daishiroh Kobayashi, Yutaka Kohmura, Toshihiko Sugiki, Eisuke Kuraoka, Masaya Denda, Toshimichi Fujiwara and Akira Otaka :
Peptide Cyclization Mediated by Metal-Free S-Arylation: S-Protected Cysteine Sulfoxide as an Umpolung of Cysteine Nucleophile,
Chemistry - A European Journal, Vol.27, No.56, 14092-14099, 2021.

(徳島大学機関リポジトリ): ● Metadata: 116324
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/chem.202102420
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1002/chem.202102420

(徳島大学機関リポジトリ: 116324, DOI: 10.1002/chem.202102420) Rina Iwase, Naoto Naruse, Miho Nakagawa, Risa Saito, Akira Shigenaga, Akira Otaka, Takahiko Hara and Kosuke Tanegashima :
Identification of Functional Domains of CXCL14 Involved in High-Affinity Binding and Intracellular Transport of CpG DNA,
The Journal of Immunology, Vol.207, No.2, 459-469, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.4049/jimmunol.2100030
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.4049/jimmunol.2100030

(DOI: 10.4049/jimmunol.2100030) Jan Vincent V. Arafiles, Hisaaki Hirose, Yusuke Hirai, Masashi Kuriyama, Maxwell Mamfe Sakyiamah, Wataru Nomura, Kazuhiro Sonomura, Miki Imanishi, Akira Otaka, Hirokazu Tamamura and Shiroh Futaki :
Discovery of a Macropinocytosis-Inducing Peptide Potentiated byMedium-Mediated Intramolecular Disulfide Formation,
Angewandte Chemie International Edition, Vol.60, No.21, 11928-11936, 2021.

(出版サイトへのリンク): ● Publication site (DOI): 10.1002/anie.202016754
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1002/anie.202016754

(DOI: 10.1002/anie.202016754) Masahiro Ueda, Chiaki Komiya, Sayuki Arii, Kohshi Kusumoto, Masaya Denda, Keiichiro Okuhira, Akira Shigenaga and Akira Otaka :
Sequence-independent traceless method for preparation of peptide/protein thioesters using CPaseY-mediated hydrazinolysis,
Chemical & Pharmaceutical Bulletin, Vol.68, No.12, 1226-1232, 2020.

(要約): Proteins incorporating artificial moieties such as fluorophores and drugs have enjoyed increasing use in chemical biology and drug development research. Preparation of such artificial protein derivatives has relied mainly on native chemical ligation in which peptide/protein thioesters chemoselectively react with N-terminal cysteine peptides to afford protein molecules. The protein thioesters derived from expressed proteins represent thioesters that are very useful for the preparation of artificial proteins by native chemical ligation with synthetic peptides with N-terminal Cys. We recently have developed a traceless thioester-producing protocol using carboxypeptidase Y (CPaseY) which is compatible with an expressed protein. The traceless character is ensured by CPaseY-mediated hydrazinolysis of C-terminal Xaa (X)-Cys-Pro-Leu-OH sequence followed by an auto-processing of the Cys-Pro (CP) dipeptide unit, affording the corresponding X-thioester (X-SR). However, hydrazinolysis of the amide bond in the prolyl leucine junction depends significantly on the nature of X. In the case of hydrophobic X residues, the hydrazinolysis overreacts to give several hydrazides while the reaction of hydrophilic X residues proceeds slowly. In this research, we attempted to develop an X-independent CPaseY-mediated protocol and found that the incorporation of a triple CP sequence into the C-terminal end (X-(CP)-Leu-OH) allows for efficient X-SR formation in a manner that is independent of X.
(キーワード): carboxypeptidase / hydrazinolysis / native chemical ligation / protein semi-synthesis / protein thioester / thioesterification
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c20-00674
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33028801; ● Search Scopus @ Elsevier (PMID): 33028801; ● Search Scopus @ Elsevier (DOI): 10.1248/cpb.c20-00674

(DOI: 10.1248/cpb.c20-00674, PubMed: 33028801) Daishiroh Kobayashi, Naoto Naruse, Masaya Denda, Akira Shigenaga and Akira Otaka :
Deprotection of S-Acetamidomethyl Cysteine with Copper (II) and 1,2-Aminothiols under Aerobic Conditions,
Organic & Biomolecular Chemistry, Vol.18, 8638-8645, 2020.

(徳島大学機関リポジトリ): ● Metadata: 115115
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/D0OB01475C
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1039/D0OB01475C

(徳島大学機関リポジトリ: 115115, DOI: 10.1039/D0OB01475C) Kento Ohkawachi, Daishiroh Kobayashi, Kyohei Morimoto, Akira Shigenaga, Masaya Denda, Kenzo Yamatsugu, Motomu Kanai and Akira Otaka :
Sulfanylmethyldimethylaminopyridine as a Useful Thiol Additive for Ligation Chemistry in Peptide/Protein Synthesis,
Organic Letters, Vol.22, No.14, 5289-5293, 2020.

(要約): Sulfanylmethyl-installed dimethylaminopyridine, 2-sulfanylmethyl-4-dimethylaminopyridine (), has an acidic thiol group comparable to that in aryl thiols due to the formation of a zwitterion consisting of a thiolate anion and a pyridinium cation. It can be used as an additive for native chemical ligation. The alkyl thiol in allows it to be used for the one-pot native chemical ligation-desulfurization protocol in peptide synthesis. The utility of in the synthesis of cyclic peptides is demonstrated.
(徳島大学機関リポジトリ): ● Metadata: 114733
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.orglett.0c01383
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32396369; ● Search Scopus @ Elsevier (PMID): 32396369; ● Search Scopus @ Elsevier (DOI): 10.1021/acs.orglett.0c01383

(徳島大学機関リポジトリ: 114733, DOI: 10.1021/acs.orglett.0c01383, PubMed: 32396369) Naoto Naruse, Daishiroh Kobayashi, Kento Ohkawachi, Akira Shigenaga and Akira Otaka :
Copper-mediated deprotection of thiazolidine and selenazolidine derivatives applied to native chemical ligation,
The Journal of Organic Chemistry, Vol.85, No.3, 1425-1433, 2020.

(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.joc.9b02388
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1021/acs.joc.9b02388

(DOI: 10.1021/acs.joc.9b02388) Atsushi Nakayama, Akira Ohtani, Tsubasa Inokuma, Daisuke Tsuji, Haruka Mukaiyama, Nakayama Akira, Kouji Itou, Akira Otaka, Tanino Keiji and Kosuke Namba :
Development of a 1,3a,6a-triazapentalene derivatives as a compact and thiol-specific fluorescent labeling reagent,
Communications Chemistry, Vol.3, 6, 2020.

(徳島大学機関リポジトリ): ● Metadata: 115071
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s42004-019-0250-0
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-85077692885

(徳島大学機関リポジトリ: 115071, DOI: 10.1038/s42004-019-0250-0, Elsevier: Scopus) Tsubasa Inokuma, Takuya Sakakibara, Takatoshi Someno, Kana Masui, Akira Shigenaga, Akira Otaka and Ken-ichi Yamada :
Asymmetric Synthesis of α-Amino Phosphonic Acids Using Stable Imino Phosphonate as a Universal Precursor,
Chemistry - A European Journal, Vol.25, 2019.

(徳島大学機関リポジトリ): ● Metadata: 115143
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/chem.201903572
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-85073945802

(徳島大学機関リポジトリ: 115143, DOI: 10.1002/chem.201903572, Elsevier: Scopus) Chiaki Komiya, Akira Shigenaga, Jun Tsukimoto, Masahiro Ueda, Takuya Morisaki, Tsubasa Inokuma, Kouji Itou and Akira Otaka :
Traceless synthesis of protein thioesters using enzyme-mediated hydrazinolysis and subsequent self-editing of cysteinyl prolyl sequence,
Chemical Communications, Vol.55, 7029-7032, 2019.

(徳島大学機関リポジトリ): ● Metadata: 113348
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/C9CC03583D
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31140482; ● Summary page in Scopus @ Elsevier: 2-s2.0-85067257026

(徳島大学機関リポジトリ: 113348, DOI: 10.1039/C9CC03583D, PubMed: 31140482, Elsevier: Scopus) Haruka Kawahara, Naoki Miyashita, Kohki Tachibana, Yusuke Tsuda, Kyohei Morimoto, Kouhei Tsuji, Akira Shigenaga, Akira Otaka, Tatsuhiro Ishida and Keiichiro Okuhira :
A photo-activatable peptide mimicking functions of apolipoprotein A-I,
Biological & Pharmaceutical Bulletin, Vol.42, No.6, 1019-1024, 2019.

(要約): Apolipoprotein A-I (apoA-I) plays a critical role in high-density lipoprotein (HDL) biogenesis, function and structural dynamics. Peptides that mimic apoA-I have a short amphipathic α-helical structure that can functionally recapitulate many of the same biologic properties of full-length apoA-I in HDL. Hence, they might be expected to have clinical applications in the reduction of atherosclerosis. However, nonspecific cellular efflux of cholesterol induced by apoA-I mimetic peptides might cause side effects that are, as yet, unidentified. In this study, we developed a photo-activatable peptide, 2F*, which is an 18 amino acid peptide mimicking apoA-I bearing an internal photocleavable caging group that is designed to assume an α-helical structure in response to a light stimulus and trigger efflux of cholesterol from cells. Without light irradiation, 2F* peptide showed a low tendency for the formation of α-helices, and therefore did not associate with lipids and failed to induce efflux of cholesterol. In addition, 2F* did not cause hemolysis under our experimental condition. Mass spectrometry indicated that, after light exposure, the caging group detached from 2F* and it assumed the α-helical structure in the presence of lipids, and enhanced cholesterol efflux from cells. Photo-activatable peptides such as 2F* that control cholesterol efflux following light stimulus may be useful for future atherosclerosis-reducing therapies.
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/bpb.b19-00114
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31155576; ● Summary page in Scopus @ Elsevier: 2-s2.0-85067107514

(DOI: 10.1248/bpb.b19-00114, PubMed: 31155576, Elsevier: Scopus) Takuya Morisaki, Akira Shigenaga and Akira Otaka :
Development of a turn-on fluorescent traceable linker employing N-sulfanylethylcoumarinyl amide for enrichment and visualization of target proteins Current Topic Drug Discovery: Recent Progress and the Future,
Chemical & Pharmaceutical Bulletin, Vol.68, No.3, 216-219, 2019.

(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c19-00726
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1248/cpb.c19-00726

(DOI: 10.1248/cpb.c19-00726) Takahisa Jichu, Tsubasa Inokuma, Keisuke Aihara, Taiki Kohiki, Kohdai Nishida, Akira Shigenaga, Ken-ichi Yamada and Akira Otaka :
A recyclable hydrophobic anchor-tagged asymmetric amino thiourea catalyst,
ChemCatChem, Vol.10, No.16, 3402-3405, 2018.

(徳島大学機関リポジトリ): ● Metadata: 111892
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cctc.201800714
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1002/cctc.201800714

(徳島大学機関リポジトリ: 111892, DOI: 10.1002/cctc.201800714) Akira Shigenaga, Naoto Naruse and Akira Otaka :
ProteoFind: A script for finding proteins that are suitable for chemical synthesis,
Tetrahedron, Vol.74, No.19, 2291-2297, 2018.

(徳島大学機関リポジトリ): ● Metadata: 111928
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2018.03.030
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tet.2018.03.030

(徳島大学機関リポジトリ: 111928, DOI: 10.1016/j.tet.2018.03.030) Tsubasa Inokuma, Kohdai Nishida, Akira Shigenaga, Ken-ichi Yamada and Akira Otaka :
Direct enantioselective indolylation of peptidyl imine for the synthesis of indolyl glycine-containing peptides,
Heterocycles, Vol.97, No.2, 1269-1287, 2018.

(出版サイトへのリンク): ● Publication site (DOI): 10.3987/COM-18-S(T)86
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.3987/COM-18-S(T)86

(DOI: 10.3987/COM-18-S(T)86) Hiroshi Inaba, Akihito Uemura, Kazushi Morishita, Taiki Kohiki, Akira Shigenaga, Akira Otaka and Kazunori Matsuura :
Light-induced propulsion of a giant liposome driven by peptide nanofibre growth,
Scientific Reports, Vol.8, No.1, articlenumber-6243, 2018.

(要約): Light-driven nano/micromotors are attracting much attention, not only as molecular devices but also as components of bioinspired robots. In nature, several pathogens such as Listeria use actin polymerisation machinery for their propulsion. Despite the development of various motors, it remains challenging to mimic natural systems to create artificial motors propelled by fibre formation. Herein, we report the propulsion of giant liposomes driven by light-induced peptide nanofibre growth on their surface. Peptide-DNA conjugates connected by a photocleavage unit were asymmetrically introduced onto phase-separated giant liposomes. Ultraviolet (UV) light irradiation cleaved the conjugates and released peptide units, which self-assembled into nanofibres, driving the translational movement of the liposomes. The velocity of the liposomes reflected the rates of the photocleavage reaction and subsequent fibre formation of the peptide-DNA conjugates. These results showed that chemical design of the light-induced peptide nanofibre formation is a useful approach to fabricating bioinspired motors with controllable motility.
(徳島大学機関リポジトリ): ● Metadata: 112429
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-018-24675-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29674666; ● Search Scopus @ Elsevier (PMID): 29674666; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-018-24675-7

(徳島大学機関リポジトリ: 112429, DOI: 10.1038/s41598-018-24675-7, PubMed: 29674666) Naoto Naruse, Kento Ohkawachi, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Resin-bound crypto-thioester for native chemical ligation,
Organic Letters, Vol.20, No.8, 2449-2453, 2018.

(徳島大学機関リポジトリ): ● Metadata: 111890
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.orglett.8b00795
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1021/acs.orglett.8b00795

(徳島大学機関リポジトリ: 111890, DOI: 10.1021/acs.orglett.8b00795) Chiharu Mizuguchi, Mitsuki Nakamura, Naoko Kurimitsu, Takashi Ohgita, Kazuchika Nishitsuji, Teruhiko Baba, Akira Shigenaga, Toshinori Shimanouchi, Keiichiro Okuhira, Akira Otaka and Hiroyuki Saito :
Effect of phosphatidylserine and cholesterol on membrane-mediated fibril formation by the N-terminal amyloidogenic fragment of apolipoprotein A-I,
Scientific Reports, Vol.8, No.1, Articlenumber-5497, 2018.

(要約): Here, we examined the effects of phosphatidylserine (PS) and cholesterol on the fibril-forming properties of the N-terminal 1-83 fragment of an amyloidogenic G26R variant of apoA-I bound to small unilamellar vesicles. A thioflavin T fluorescence assay together with microscopic observations showed that PS significantly retards the nucleation step in fibril formation by apoA-I 1-83/G26R, whereas cholesterol slightly enhances fibril formation. Circular dichroism analyses demonstrated that PS facilitates a structural transition from random coil to α-helix in apoA-I 1-83/G26R with great stabilization of the α-helical structure upon lipid binding. Isothermal titration calorimetry measurements revealed that PS induces a marked increase in capacity for binding of apoA-I 1-83/G26R to the membrane surface, perhaps due to electrostatic interactions of positively charged amino acids in apoA-I with PS. Such effects of PS to enhance lipid interactions and inhibit fibril formation of apoA-I were also observed for the amyloidogenic region-containing apoA-I 8-33/G26R peptide. Fluorescence measurements using environment-sensitive probes indicated that PS induces a more solvent-exposed, membrane-bound conformation in the amyloidogenic region of apoA-I without affecting membrane fluidity. Since cell membranes have highly heterogeneous lipid compositions, our findings may provide a molecular basis for the preferential deposition of apoA-I amyloid fibrils in tissues and organs.
(徳島大学機関リポジトリ): ● Metadata: 112401
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-018-23920-3
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29615818; ● Search Scopus @ Elsevier (PMID): 29615818; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-018-23920-3

(徳島大学機関リポジトリ: 112401, DOI: 10.1038/s41598-018-23920-3, PubMed: 29615818) Akira Otaka :
Current Topics - Drug Discovery: Recent Progress and the Future Foreward,
Chemical & Pharmaceutical Bulletin, Vol.66, No.3, 189-190, 2018.

(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c18-ctf6603
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1248/cpb.c18-ctf6603

(DOI: 10.1248/cpb.c18-ctf6603) Kosuke Tanegashima, Rena Takahashi, Hideko Nuriya, Naoto Naruse, Kohei Tsuji, Akira Shigenaga, Akira Otaka and Takahiko Hara :
CXCL14 acts as a specific carrier of CpG into dendritic cells and activates Toll-like receptor 9-mediated adaptive immunity,
EBioMedicine, Vol.24, 247-256, 2017.

(要約): CXCL14 is a primordial chemokine that plays multiple roles in tumor suppression, autoimmune arthritis, and obesity-associated insulin resistance. However, the underlying molecular mechanisms are unclear. Here, we show that CXCL14 transports various types of CpG oligodeoxynucleotide (ODN) into the endosomes and lysosomes of bone marrow-derived dendritic cells (DCs), thereby activating Toll-like receptor 9 (TLR9). A combination of CpG ODN (ODN2395) plus CXCL14 induced robust production of IL-12 p40 by wild-type, but not Tlr9-knockout, DCs. Consistent with this, ODN2395-mediated activation of DCs was significantly attenuated in Cxcl14-knockout mice. CXCL14 bound CpG ODN with high affinity at pH7.5, but not at pH6.0, thereby enabling efficient delivery of CpG ODN to TLR9 in the endosome/lysosome. Furthermore, the CXCL14-CpG ODN complex specifically bound to high affinity CXCL14 receptors on DCs. Thus, CXCL14 serves as a specific carrier of CpG DNA to sensitize TLR9-mediated immunosurveillance.
(徳島大学機関リポジトリ): ● Metadata: 115089
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.ebiom.2017.09.012
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28928016; ● Summary page in Scopus @ Elsevier: 2-s2.0-85029518057

(徳島大学機関リポジトリ: 115089, DOI: 10.1016/j.ebiom.2017.09.012, PubMed: 28928016, Elsevier: Scopus) Taiki Kohiki, Yusuke Nishikawa, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Chemical synthetic platform for chlorpromazine oligomers that were reported as photo-degradation products of chlorpromazine,
Chemical & Pharmaceutical Bulletin, Vol.65, No.12, 1161-1166, 2017.

(要約): A synthetic platform for chlorpromazine (CPZ) oligomers, which could be generated via photo-reaction of CPZ, is essential to promote their biological and structural studies. In this paper, the first synthetic platform for CPZ oligomers is described. A photo-irradiation experiment of CPZ to confirm whether the structure of the CPZ dimer generated by the photo-irradiation was identical to that prepared by our synthetic method is also reported.
(キーワード): Chlorpromazine / Chromatography, High Pressure Liquid / Dimerization / Isomerism / Mass Spectrometry / Photolysis / Polymerization / Ultraviolet Rays
(徳島大学機関リポジトリ): ● Metadata: 111929
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c17-00692
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 29199220; ● Summary page in Scopus @ Elsevier: 2-s2.0-85038427787

(徳島大学機関リポジトリ: 111929, DOI: 10.1248/cpb.c17-00692, PubMed: 29199220, Elsevier: Scopus) Keisuke Aihara, Tsubasa Inokuma, Takahisa Jichu, Zhenjian Lin, Feixue Fu, Kosuke Yamaoka, Akira Shigenaga, David A. Hutchins, Eric W. Schmidt and Akira Otaka :
Cysteine-free intramolecular ligaiton of N-sulfanylethylanilide peptide using 4-mercaptobenzylphosphonic acid: Synthesis of cyclic peptide, trichamide,
Synlett, Vol.28, No.15, 1944-1949, 2017.

(徳島大学機関リポジトリ): ● Metadata: 111889
(出版サイトへのリンク): ● Publication site (DOI): 10.1055/s-0036-1589055
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1055/s-0036-1589055

(徳島大学機関リポジトリ: 111889, DOI: 10.1055/s-0036-1589055) Tetsuro Yoshimaru, Keisuke Aihara, Masato Komatsu, Yosuke Matsushita, Yasumasa Okazaki, Shinya Toyokuni, Junko Honda, Mitsunori Sasa, Yasuo Miyoshi, Akira Otaka and Toyomasa Katagiri :
Stapled BIG3 helical peptide ERAP potentiates anti-tumour activity for breast cancer therapeutics.,
Scientific Reports, Vol.7, No.1, 1821, 2017.

(要約): Estradiol (E2) and the oestrogen receptor-alpha (ER) signalling pathway play pivotal roles in the proliferative activity of breast cancer cells. Recent findings show that the brefeldin A-inhibited guanine nucleotide-exchange protein 3-prohibitin 2 (BIG3-PHB2) complex plays a crucial role in E2/ER signalling modulation in breast cancer cells. Moreover, specific inhibition of the BIG3-PHB2 interaction using the ER activity-regulator synthetic peptide (ERAP: 165-177 amino acids), derived from -helical BIG3 sequence, resulted in a significant anti-tumour effect. However, the duration of this effect was very short for viable clinical application. We developed the chemically modified ERAP using stapling methods (stapledERAP) to improve the duration of its antitumour effects. The stapledERAP specifically inhibited the BIG3-PHB2 interaction and exhibited long-lasting suppressive activity. Its intracellular localization without the membrane-permeable polyarginine sequence was possible via the formation of a stable -helix structure by stapling. Tumour bearing-mice treated daily or weekly with stapledERAP effectively prevented the BIG3-PHB2 interaction, leading to complete regression of E2-dependent tumours in vivo. Most importantly, combination of stapledERAP with tamoxifen, fulvestrant, and everolimus caused synergistic inhibitory effects on growth of breast cancer cells. Our findings suggested that the stapled ERAP may be a promising anti-tumour drug to suppress luminal-type breast cancer growth.
(徳島大学機関リポジトリ): ● Metadata: 112387
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/s41598-017-01951-6
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28500289; ● Search Scopus @ Elsevier (PMID): 28500289; ● Search Scopus @ Elsevier (DOI): 10.1038/s41598-017-01951-6

(徳島大学機関リポジトリ: 112387, DOI: 10.1038/s41598-017-01951-6, PubMed: 28500289) Taiki Kohiki, Yusuke Kato, Yusuke Nishikawa, Kazuko YORITA, Ikuko Sagawa, Masaya Denda, Tsubasa Inokuma, Akira Shigenaga, Kiyoshi Fukui and Akira Otaka :
Inside Front Cover: Elucidation of inhibitor-binding pocket of D-amino acid oxidase using docking simulation and N-sulfanylethylanilide-based labeling technology,
Organic & Biomolecular Chemistry, Vol.15, 5240, 2017.

(出版サイトへのリンク): ● Publication site (DOI): 10.1039/C7OB90109G
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1039/C7OB90109G

(DOI: 10.1039/C7OB90109G) Taiki Kohiki, Yusuke Kato, Yusuke Nishikawa, Kazuko YORITA, Ikuko Sagawa, Masaya Denda, Tsubasa Inokuma, Akira Shigenaga, Kiyoshi Fukui and Akira Otaka :
Elucidation of inhibitor-binding pocket of D-amino acid oxidase using docking simulation and N-sulfanylethylanilide-based labeling technology,
Organic & Biomolecular Chemistry, Vol.15, No.25, 5289-5297, 2017.

(徳島大学機関リポジトリ): ● Metadata: 111927
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/C7OB00633K
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1039/C7OB00633K

(徳島大学機関リポジトリ: 111927, DOI: 10.1039/C7OB00633K) Akiko Yano, Yuko Takahashi, Hiromi Moriguchi, Tomoaki Inazumi, Tomoaki Koga, Akira Otaka, Yukihiko Sugimoto and Hironobu Hojo :
An aromatic amino acid within intracellular loop 2 of the prostaglandin EP2 receptor is a prerequisite for selective association and activation of Gas,
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Vol.1862, No.6, 615-622, 2017.

(要約): We previously demonstrated that the aromatic moiety of Tyr(143) within the intracellular loop 2 (ICL2) region of the prostaglandin EP2 receptor plays a crucial role in Gs coupling. Here we investigated whether the ICL2 of the EP2 receptor directly binds to Gs and whether an aromatic moiety affects this interaction. In Chinese hamster ovary cells, mutations of Tyr(143) reduced the ability of the EP2 receptor to interact with G proteins as demonstrated by GTPS sensitivity, as well as the ability of agonist-induced cAMP formation, with the rank order of Phe>Tyr (wild-type)=Trp>Leu>Ala (=0). We found that the wild-type ICL2 peptide (i2Y) and its mutant with Phe at Tyr(143) (i2F) inhibited receptor-G protein complex formation of wild-type EP2 in membranes, whereas the Ala-substituted mutant (i2A) did not. Specific interactions between these peptides and the Gs protein were detected by surface plasmon resonance, but Gs showed different association rates, with a rank order of i2F>i2Yi2A, with similar dissociation rates. Moreover, i2F and i2Y, but not i2A activated membrane adenylyl cyclase. These results indicate that the ICL2 region of the EP2 receptor is its potential interaction site with Gs, and that the aromatic side chain moiety at position 143 is a determinant for the accessibility of the ICL2 to the Gs protein.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbalip.2017.03.006
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28336329; ● Search Scopus @ Elsevier (PMID): 28336329; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbalip.2017.03.006

(DOI: 10.1016/j.bbalip.2017.03.006, PubMed: 28336329) Tsubasa Inokuma, Takahisa Jichu, Kodai Nishida, Akira Shigenaga and Akira Otaka :
A convenient method for preparation of -imino carboxylic acid derivatives and application to the asymmetric synthesis of unnatural -amino acid derivative,
Chemical & Pharmaceutical Bulletin, Vol.65, No.6, 573-581, 2017.

(要約): We describe herein a manganese(IV) oxide-mediated oxidation of N-p-methoxyphenyl (PMP)-protected glycine derivatives for the synthesis of -imino carboxylic acid derivatives. Using this methodology, utilization of unstable glyoxic acid derivatives was avoided. Furthermore, using this methodology we synthesized novel -imino carboxylic acid derivatives such as -imino phenyl ester, perfluoroalkyl etsers, imides, and thioester. The asymmetric Mannich reaction of those novel imine derivatives with 1,3-dicarbonyl compound is also described, and the novel -imino imide gave improved chemical yield and stereoselectivity compared with those obtained by the use of the conventional -imino ester-type substrate.
(キーワード): Amino Acids / Carbon-13 Magnetic Resonance Spectroscopy / Carboxylic Acids / Imino Acids / Proton Magnetic Resonance Spectroscopy / Spectrometry, Mass, Electrospray Ionization
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c17-00158
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28566650; ● Search Scopus @ Elsevier (PMID): 28566650; ● Search Scopus @ Elsevier (DOI): 10.1248/cpb.c17-00158

(DOI: 10.1248/cpb.c17-00158, PubMed: 28566650) Shugo Tsuda, Masayoshi Mochizuki, Ken Sakamoto, Masaya Denda, Hideki Nishio, Akira Otaka and Taku Yoshiya :
N-Sulfanylethylaminooxybutyramide (SEAoxy): A Crypto-Thioester Compatible with Fmoc Solid-Phase Peptide Synthesis,
Organic Letters, Vol.18, No.22, 5940-5943, 2016.

(要約): An N-sulfanylethylaminooxybutyramide (SEAoxy) has been developed as a novel thioester equivalent for native chemical ligation. SEAoxy peptide was straightforwardly synthesized by conventional Fmoc solid-phase peptide synthesis without a problem. Moreover, SEAoxy peptide could be directly applied to native chemical ligation owing to the intramolecular N-to-S acyl shift that releases the peptide-thioester in situ. This methodology was successfully applied to the synthesis of two bioactive peptides.
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.orglett.6b03055
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27805411; ● Search Scopus @ Elsevier (PMID): 27805411; ● Search Scopus @ Elsevier (DOI): 10.1021/acs.orglett.6b03055

(DOI: 10.1021/acs.orglett.6b03055, PubMed: 27805411) Shiho Mikawa, Chiharu Mizuguchi, Kazuchika Nishitsuji, Teruhiko Baba, Akira Shigenaga, Toshinori Shimanouchi, Naomi Sakashita, Akira Otaka, Kenichi Akaji and Hiroyuki Saito :
Heparin promotes fibril formation of the N-terminal fragment of amyloidogenic aplipoprotein A-I,
FEBS Letters, Vol.590, 3492-3500, 2016.

(要約): Glycosaminoglycans are known to be associated with extracellular amyloid deposits of various amyloidogenic proteins. In this study, we found that the glycosaminoglycan heparin greatly accelerates the elongation step in fibril formation by the N-terminal 1-83 fragment of human apolipoprotein A-I (apoA-I), especially in the amyloidogenic W50R variant. Using fragment peptides, we demonstrate that heparin significantly promotes β-transition and fibril formation of the highly amyloidogenic region spanning residues 44-65 and colocalizes with fibrils formed by the W50R variant. These results suggest the possible role of glycosaminoglycans in fibril formation by amyloidogenic apoA-I variants.
(キーワード): Amyloid / Apolipoprotein A-I / Circular Dichroism / Humans / Microscopy, Atomic Force / Peptide Fragments / Point Mutation / Protein Conformation / Protein Structure, Secondary / Spectroscopy, Fourier Transform Infrared
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/1873-3468.12426
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27654470; ● Summary page in Scopus @ Elsevier: 2-s2.0-84992473194

(DOI: 10.1002/1873-3468.12426, PubMed: 27654470, Elsevier: Scopus) Mitsuhiro Eto, Naoto Naruse, Kyohei Morimoto, Kosuke Yamaoka, Kohei Sato, Kohei Tsuji, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Development of an anilide-type scaffold for the thioester precursor N-sulfanylethylcoumarinyl amide,
Organic Letters, Vol.18, No.17, 4416-4419, 2016.

(要約): N-Sulfanylethylcoumarinyl amide (SECmide) peptide, which was initially developed for use in the fluorescence-guided detection of promoters of N-S acyl transfer, was successfully applied to a facile and side reaction-free protocol for N-S acyl-transfer-mediated synthesis of peptide thioesters. Additionally, 4-mercaptobenzylphosphonic acid (MBPA) was proven to be a useful catalyst for the SECmide or N-sulfanylethylanilide (SEAlide)-mediated NCL reaction.
(徳島大学機関リポジトリ): ● Metadata: 111879
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.orglett.6b02207
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27529363; ● Search Scopus @ Elsevier (PMID): 27529363; ● Search Scopus @ Elsevier (DOI): 10.1021/acs.orglett.6b02207

(徳島大学機関リポジトリ: 111879, DOI: 10.1021/acs.orglett.6b02207, PubMed: 27529363) Takahiro Nakamura, Kohei Sato, Naoto Naruse, Keisuke Kitakaze, Tsubasa Inokuma, Takatsugu Hirokawa, Akira Shigenaga, Kouji Itou and Akira Otaka :
Back Cover: Tailored synthesis of 162-residue S-monoglycosylated GM2-activator protein (GM2AP) analogues that allows access to protein library,
ChemBioChem, Vol.17, No.20, 1994, 2016.

(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cbic.201600521
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1002/cbic.201600521

(DOI: 10.1002/cbic.201600521) Takahiro Nakamura, Kohei Sato, Naoto Naruse, Keisuke Kitakaze, Tsubasa Inokuma, Takatsugu Hirokawa, Akira Shigenaga, Kouji Itou and Akira Otaka :
Tailored synthesis of 162-residue S-monoglycosylated GM2-activator protein (GM2AP) analogues that allows access to protein library,
ChemBioChem, Vol.17, No.20, 1986-1992, 2016.

(徳島大学機関リポジトリ): ● Metadata: 111880
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cbic.201600400
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27428709; ● Summary page in Scopus @ Elsevier: 2-s2.0-84991661622

(徳島大学機関リポジトリ: 111880, DOI: 10.1002/cbic.201600400, PubMed: 27428709, Elsevier: Scopus) Masaya Denda, Takuya Morisaki, Taiki Kohiki, Jun Yamamoto, Kohei Sato, Ikuko Sagawa, Tsubasa Inokuma, Youichi Sato, Aiko Yamauchi, Akira Shigenaga and Akira Otaka :
Labelling of endogenous target protein via N-S acyl transfer-mediated activation of N-sulfanylethylanilide,
Organic & Biomolecular Chemistry, Vol.14, 6244-6251, 2016.

(徳島大学機関リポジトリ): ● Metadata: 111885
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/C6OB01014H
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1039/C6OB01014H

(徳島大学機関リポジトリ: 111885, DOI: 10.1039/C6OB01014H) Takuya Morisaki, Masaya Denda, Jun Yamamoto, Daisuke Tsuji, Kouji Itou, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
An N-Sulfanylethylanilide-based traceable linker for enrichment and selective labelling of target proteins,
Chemical Communications, Vol.52, 6911-6913, 2016.

(徳島大学機関リポジトリ): ● Metadata: 111925
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/C6CC01229A
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1039/C6CC01229A

(徳島大学機関リポジトリ: 111925, DOI: 10.1039/C6CC01229A) Tatsuhiko Shimizu, Rin Miyajima, Naoto Naruse, Kosuke Yamaoka, Keisuke Aihara, Akira Shigenaga and Akira Otaka :
Facile preparation of peptides with C-terminal N-alkylamide via radical-initiated dethiocarboxylation,
Chemical & Pharmaceutical Bulletin, Vol.64, No.4, 375-378, 2016.

(要約): A new synthetic method has been developed to prepare peptides bearing a C-terminal N-alkylamide from peptide thioacids via a radical-initiated dethiocarboxylation process. This method enables the introduction of various alkyl groups to C-terminal amides simply by replacing the amino acid building block. Its application to the preparation of anti-cancer drug ABT-510 is also reported.
(徳島大学機関リポジトリ): ● Metadata: 111926
(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c15-01025
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27039836; ● Summary page in Scopus @ Elsevier: 2-s2.0-84964768936

(徳島大学機関リポジトリ: 111926, DOI: 10.1248/cpb.c15-01025, PubMed: 27039836, Elsevier: Scopus) Yuki Haraya, Ryo Nadai, Hitoshi Kimura, Kazuchika Nishitsuji, Kenji Uchimura, Kumiko Sakai-Kato, Kohsaku Kawakami, Akira Shigenaga, Toru Kawakami, Akira Otaka, Hironobu Hojo, Naomi Sakashita and Hiroyuki Saito :
Enthalpy-driven interactions with sulfated glycosaminoglycans promote cell membrane penetration of arginine peptides,
Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol.1858, No.6, 1339-1349, 2016.

(要約): The first step of cell membrane penetration of arginine peptides is thought to occur via electrostatic interactions between positive charges of arginine residues and negative charges of sulfated glycosaminoglycans (GAGs) on the cell surface. However, the molecular interaction of arginine peptides with GAG still remains unclear. Here, we compared the interactions of several arginine peptides of Tat, R8, and Rev and their analogues with heparin in relation to the cell membrane penetration efficiency. The high-affinity binding of arginine peptides to heparin was shown to be driven by large favorable enthalpy contributions, possibly reflecting multidentate hydrogen bondings of arginine residues with sulfate groups of heparin. Interestingly, the lysine peptides in which all arginine residues are substituted with lysine residues exhibited negligible binding enthalpy despite of their considerable binding to heparin. In CHO-K1 cells, arginine peptides exhibited a great cell-penetrating ability whereas their corresponding lysine peptides did not penetrate into cells. The degree of cell penetration of arginine peptides markedly decreased by the chlorate treatment of cells which prevents the sulfation of GAG chains. Significantly, the cell penetration efficiency of arginine peptides was found to be correlated with the favorable enthalpy of binding to heparin. These results suggest that the enthalpy-driven strong interaction with sulfated GAGs such as heparan sulfate plays a critical role in the efficient cell membrane penetration of arginine peptides.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbamem.2016.03.021
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27003128; ● Summary page in Scopus @ Elsevier: 2-s2.0-84962429271

(DOI: 10.1016/j.bbamem.2016.03.021, PubMed: 27003128, Elsevier: Scopus) Yukihiro Itoh, Keisuke Aihara, Paolo Mellini, Toshifumi Tojo, Yosuke Ota, Hiroki Tsumoto, Viswas Raja Solomon, Peng Zhan, Miki Suzuki, Daisuke Ogasawara, Akira Shigenaga, Tsubasa Inokuma, Hidehiko Nakagawa, Naoki Miyata, Tamio Mizukami, Akira Otaka and Takayoshi Suzuki :
Identification of SNAIL1 Peptide-Based Irreversible Lysine Specific Demethylase 1-Selective Inactivators,
Journal of Medicinal Chemistry, Vol.59, No.4, 1531-1544, 2016.

(要約): Inhibition of lysine-specific demethylase 1 (LSD1), a flavin-dependent histone demethylase, has recently emerged as a new strategy for treating cancer and other diseases. LSD1 interacts physically with SNAIL1, a member of the SNAIL/SCRATCH family of transcription factors. This study describes the discovery of SNAIL1 peptide-based inactivators of LSD1. We designed and prepared SNAIL1 peptides bearing a propargyl amine, hydrazine, or phenylcyclopropane moiety. Among them, peptide 3, bearing hydrazine, displayed the most potent LSD1-inhibitory activity in enzyme assays. Kinetic study and mass spectrometric analysis indicated that peptide 3 is a mechanism-based LSD1 inhibitor. Furthermore, peptides 37 and 38, which consist of cell-membrane-permeable oligoarginine conjugated with peptide 3, induced a dose-dependent increase of dimethylated Lys4 of histone H3 in HeLa cells, suggesting that they are likely to exhibit LSD1-inhibitory activity intracellularly. In addition, peptide 37 decreased the viability of HeLa cells. We believe this new approach for targeting LSD1 provides a basis for development of potent selective inhibitors and biological probes for LSD1.
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.jmedchem.5b01323
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26700437; ● Search Scopus @ Elsevier (PMID): 26700437; ● Search Scopus @ Elsevier (DOI): 10.1021/acs.jmedchem.5b01323

(DOI: 10.1021/acs.jmedchem.5b01323, PubMed: 26700437) Kitakaze Keisuke, Mizutani Yasumichi, Sugiyama Eiji, Tasaki Chikako, Daisuke Tsuji, Nobuo Maita, Hirokawa Takatsugu, Asanuma Daisuke, Kamiya Mako, Sato Kohei, Setou Mitsutoshi, Urano Yasuteru, Togawa Tadayasu, Akira Otaka, Sakuraba Hitoshi and Kouji Itou :
Protease-resistant modified human β-hexosaminidase B ameliorates symptoms in GM2 gangliosidosis model,
The Journal of Clinical Investigation, Vol.126, No.5, 1691-1703, 2016.

(要約): GM2 gangliosidoses, including Tay-Sachs and Sandhoff diseases, are neurodegenerative lysosomal storage diseases that are caused by deficiency of β-hexosaminidase A, which comprises an αβ heterodimer. There are no effective treatments for these diseases; however, various strategies aimed at restoring β-hexosaminidase A have been explored. Here, we produced a modified human hexosaminidase subunit β (HexB), which we have termed mod2B, composed of homodimeric β subunits that contain amino acid sequences from the α subunit that confer GM2 ganglioside-degrading activity and protease resistance. We also developed fluorescent probes that allow visualization of endocytosis of mod2B via mannose 6-phosphate receptors and delivery of mod2B to lysosomes in GM2 gangliosidosis models. In addition, we applied imaging mass spectrometry to monitor efficacy of this approach in Sandhoff disease model mice. Following i.c.v. administration, mod2B was widely distributed and reduced accumulation of GM2, asialo-GM2, and bis(monoacylglycero)phosphate in brain regions including the hypothalamus, hippocampus, and cerebellum. Moreover, mod2B administration markedly improved motor dysfunction and a prolonged lifespan in Sandhoff disease mice. Together, the results of our study indicate that mod2B has potential for intracerebrospinal fluid enzyme replacement therapy and should be further explored as a gene therapy for GM2 gangliosidoses.
(出版サイトへのリンク): ● Publication site (DOI): 10.1172/JCI85300
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 27018595; ● Search Scopus @ Elsevier (PMID): 27018595; ● Search Scopus @ Elsevier (DOI): 10.1172/JCI85300

(DOI: 10.1172/JCI85300, PubMed: 27018595) Tatsuhiko Shimizu, Rin Miyajima, Kohei Sato, Ken Sakamoto, Naoto Naruse, Miku Kita, Akira Shigenaga and Akira Otaka :
Facile synthesis of C-terminal peptide thioacids under mild conditions from N-sulfanylethylanilide peptides,
Tetrahedron, Vol.72, 992-998, 2016.

(徳島大学機関リポジトリ): ● Metadata: 111924
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2015.12.070
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tet.2015.12.070

(徳島大学機関リポジトリ: 111924, DOI: 10.1016/j.tet.2015.12.070) Hirokazu Kariyazono, Ryo Nadai, Rin Miyajima, Yuki Haraya, Teruhiko Baba, Akira Shigenaga, Keiichiro Okuhira, Akira Otaka and Hiroyuki Saito :
Formation of stable nanodiscs by bihelical apolipoprotein A-I mimetic peptide,
Journal of Peptide Science, Vol.22, No.2, 116-122, 2016.

(要約): Nanodiscs are composed of scaffold protein or peptide such as apolipoprotein A-I (apoA-I) and phospholipids. Although peptide-based nanodiscs have an advantage to modulate the size of nanodiscs by changing phospholipid/peptide ratios, they are usually less stable than apoA-I-based nanodiscs. In this study, we designed a novel nanodisc scaffold peptide (NSP) that has proline-punctuated bihelical amphipathic structure based on apoA-I mimetic peptides. NSP formed -helical structure on 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) nanodiscs prepared by cholate dialysis method. Dynamic light scattering measurements demonstrated that diameters of NSP nanodiscs vary depending upon POPC/NSP ratios. Comparison of thermal unfolding of nanodiscs monitored by circular dichroism measurements demonstrated that NSP forms much more stable nanodiscs with POPC than monohelical peptide, 4F, exhibiting comparable stability to apoA-I-POPC nanodiscs. Intrinsic Trp fluorescence measurements showed that Trp residues of NSP exhibit more hydrophobic environment than that of 4 F on nanodiscs, suggesting the stronger interaction of NSP with phospholipids. Thus, the bihelical structure of NSP appears to increase the stability of nanodiscs because of the enhanced interaction of peptides with phospholipids. In addition, NSP as well as 4F spontaneously solubilized POPC vesicles into nanodiscs without using detergent. These results indicate that bihelical NSP forms nanodiscs with comparable stability to apoA-I and has an ability to control the size of nanodiscs simply by changing phospholipid/peptide ratios. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/psc.2847
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26780967; ● Summary page in Scopus @ Elsevier: 2-s2.0-84957309003

(DOI: 10.1002/psc.2847, PubMed: 26780967, Elsevier: Scopus) Chiaki Komiya, Keisuke Aihara, Kou Morishita, Hao Ding, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Development of an intein-inspired amide cleavage chemical device,
The Journal of Organic Chemistry, Vol.81, No.2, 699-707, 2016.

(要約): A photoresponsive amide cleavage device was developed based on the asparagine imidation-mediated cleavage of peptide bonds during intein-mediated protein splicing. The chemical environment of the protein splicing process was mimicked by the incorporation of geminal dimethyl groups and a secondary amine unit in asparagine scaffold. Furthermore, the resulting photoresponsive device could induce the phototriggered cleavage of an amide bond by the protection of the secondary amine unit with an o-nitrobenzyloxycarbonyl group.
(徳島大学機関リポジトリ): ● Metadata: 111896
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.joc.5b02399
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26646813; ● Search Scopus @ Elsevier (PMID): 26646813; ● Search Scopus @ Elsevier (DOI): 10.1021/acs.joc.5b02399

(徳島大学機関リポジトリ: 111896, DOI: 10.1021/acs.joc.5b02399, PubMed: 26646813) Keisuke Aihara, Kosuke Yamaoka, Naoto Naruse, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
One-pot/sequential native chemical ligation using photo-caged crypto-thioester,
Organic Letters, Vol.18, No.3, 596-599, 2016.

(要約): A practical and efficient methodology for the chemical synthesis of peptides/proteins using a one-pot/sequential ligation is described. It features the use of photocleavable S-protection on an N-sulfanylethylaniline moiety. Removal of the S-protecting ligated materials under UV irradiation provides a readily usable mixture for subsequent native chemical ligation.
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.orglett.5b03661
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26753720; ● Search Scopus @ Elsevier (PMID): 26753720; ● Search Scopus @ Elsevier (DOI): 10.1021/acs.orglett.5b03661

(DOI: 10.1021/acs.orglett.5b03661, PubMed: 26753720) Rin Miyajima, Yusuke Tsuda, Tsubasa Inokuma, Akira Shigenaga, Miki Imanishi, Shiro Futaki and Akira Otaka :
Preparation of peptide thioesters from naturally occurring sequences using reaction sequence consisting of regioselective S-cyanylation and hydrazinolysis,
Biopolymers, Vol.106, No.4, 531-546, 2015.

(要約): The vital roles of peptide/protein thioesters in protein chemistry, including chemical or semi-synthesis of proteins, have encouraged studies on the development of methods for the preparation of such chemical units. Biochemical protocols using intein or sortase have proved to be useful in protein chemistry as methods suitable for naturally occurring sequences, including recombinant proteins. Although chemical protocols are potential options for thioester preparation, only a few are applicable to naturally occurring sequences, because standard chemical protocols require an artificial chemical device for producing thioesters. In this context, the chemical preparation of thioesters based on a reaction sequence consisting of regioselective S-cyanylation and hydrazinolysis was investigated. Regioselective S-cyanylation, which is required for cysteine-containing thioesters, was achieved with the aid of a zinc-complex formation of a CCHH-type zinc-finger sequence. Free cysteine residues that are not involved in complex formation were selectively protected with a 6-nitroveratryl group followed by S-cyanylation of the zinc-binding cysteine. Hydrazinolysis of the resulting S-cyanopeptide and subsequent photo-removal of the 6-nitroveratryl group yielded the desired peptide hydrazide, which was then converted to the corresponding thioester. The generated thioester was successfully used in N-to-C-directed one-pot/sequential native chemical ligation using an N-sulfanylethylanilide peptide to give a 64-residue peptide toxin. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 531-546, 2016.
(徳島大学機関リポジトリ): ● Metadata: 111898
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/bip.22757
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26501985; ● Search Scopus @ Elsevier (PMID): 26501985; ● Search Scopus @ Elsevier (DOI): 10.1002/bip.22757

(徳島大学機関リポジトリ: 111898, DOI: 10.1002/bip.22757, PubMed: 26501985) Chiharu Mizuguchi, Fuka Ogata, Shiho Mikawa, Kohei Tsuji, Teruhiko Baba, Akira Shigenaga, Toshinori Shimanouchi, Keiichiro Okuhira, Akira Otaka and Hiroyuki Saito :
Amyloidogenic Mutation Promotes Fibril Formation of the N-terminal Apolipoprotein A-I on Lipid Membranes,
The Journal of Biological Chemistry, Vol.290, No.34, 20947-20959, 2015.

(要約): The N-terminal amino acid 1-83 fragment of apolipoprotein A-I (apoA-I) has a strong propensity to form amyloid fibrils at physiological neutral pH. Because apoA-I has an ability to bind to lipid membranes, we examined the effects of the lipid environment on fibril-forming properties of the N-terminal fragment of apoA-I variants. Thioflavin T fluorescence assay as well as fluorescence and transmission microscopies revealed that upon lipid binding, fibril formation by apoA-I 1-83 is strongly inhibited, whereas the G26R mutant still retains the ability to form fibrils. Such distinct effects of lipid binding on fibril formation were also observed for the amyloidogenic prone region-containing peptides, apoA-I 8-33 and 8-33/G26R. This amyloidogenic region shifts from random coil to -helical structure upon lipid binding. The G26R mutation appears to prevent this helix transition because lower helical propensity and more solvent-exposed conformation of the G26R variant upon lipid binding were observed in the apoA-I 1-83 fragment and 8-33 peptide. With a partially -helical conformation induced by the presence of 2,2,2-trifluoroethanol, fibril formation by apoA-I 1-83 was strongly inhibited, whereas the G26R variant can form amyloid fibrils. These findings suggest a new possible pathway for amyloid fibril formation by the N-terminal fragment of apoA-I variants: the amyloidogenic mutations partially destabilize the -helical structure formed upon association with lipid membranes, resulting in physiologically relevant conformations that allow fibril formation.
(キーワード): Amyloid / Apolipoprotein A-I / Escherichia coli / Fluorescent Dyes / Gene Expression / Humans / Mutation / Phosphatidylcholines / Protein Binding / Protein Engineering / Protein Structure, Secondary / Protein Structure, Tertiary / Recombinant Fusion Proteins / Structure-Activity Relationship / Thiazoles / Trifluoroethanol / Unilamellar Liposomes
(出版サイトへのリンク): ● Publication site (DOI): 10.1074/jbc.M115.664227
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26175149; ● Search Scopus @ Elsevier (PMID): 26175149; ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M115.664227

(DOI: 10.1074/jbc.M115.664227, PubMed: 26175149) Kohei Tsuji, Kosuke Tanegashima, Kohei Sato, Ken Sakamoto, Akira Shigenaga, Tsubasa Inokuma, Takahiko Hara and Akira Otaka :
Efficient one-pot synthesis of CXCL14 and its derivative using an N-sulfanylethylanilide peptide as a peptide thioester equivalent and their biological evaluation,
Bioorganic & Medicinal Chemistry, Vol.23, No.17, 5909-5914, 2015.

(要約): CXCL14 is a CXC-type chemokine that exhibits chemotactic activity for immature dendritic cells, activated macrophages, and activated natural killer cells. However, its specific receptor and signaling pathway remain obscure. Recently, it was reported that CXCL14 binds to CXCR4 with high affinity and inhibits CXCL12-mediated chemotaxis. Furthermore, the CXCL14 C-terminal -helical region is important for binding to its receptor. In this context, we chemically synthesized CXCL14 and its derivative with a one-pot method using N-sulfanylethylanilide peptide as a thioester equivalent. The synthetic CXCL14 proteins possessed inhibitory activities to CXCL12-mediated chemotaxis comparable with that of recombinant CXCL14. Moreover, we proved that chemically biotinylated CXCL14 binds to CXCR4 on cells by flow cytometry analysis.
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bmc.2015.06.064
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26187016; ● Summary page in Scopus @ Elsevier: 2-s2.0-84946151058

(DOI: 10.1016/j.bmc.2015.06.064, PubMed: 26187016, Elsevier: Scopus) Koji Takagi, Hayato Fukuda, Satoshi Syuto, Akira Otaka and Mitsuhiro Arisawa :
Safe removal of the allyl protecting groups of allyl esters using a recyclable, low-leaching and ligand-free palladium nanoparticle Catalyst,
Advanced Synthesis & Catalysis, Vol.357, No.9, 2119-2124, 2015.

(出版サイトへのリンク): ● Publication site (DOI): 10.1002/adsc.201500055
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-85027936276

(DOI: 10.1002/adsc.201500055, Elsevier: Scopus) Miku Kita, Jun Yamamoto, Takuya Morisaki, Chiaki Komiya, Tsubasa Inokuma, Licht Miyamoto, Koichiro Tsuchiya, Akira Shigenaga and Akira Otaka :
Design and synthesis of a hydrogen peroxide-responsive amino acid that induces peptide bond cleavage after exposure to hydrogen peroxide,
Tetrahedron Letters, Vol.56, No.28, 4228-4231, 2015.

(徳島大学機関リポジトリ): ● Metadata: 111909
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tetlet.2015.05.060
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-84930930016

(徳島大学機関リポジトリ: 111909, DOI: 10.1016/j.tetlet.2015.05.060, Elsevier: Scopus) Deokho Jung, Kohei Sato, Kyougmi Min, Akira Shigenaga, Juyeon Jung, Akira Otaka and Youngeun Kwon :
Photo-triggered fluorescent labelling of recombinant proteins in live cells,
Chemical Communications, Vol.51, No.47, 9670-9673, 2015.

(要約): A method to photo-chemically trigger fluorescent labelling of proteins in live cells is developed. The approach is based on photo-caged split-intein mediated conditional protein trans-splicing reaction and enabled background-free fluorescent labelling of target proteins with the necessary spatiotemporal control.
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/C5CC01067E
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25977944; ● Summary page in Scopus @ Elsevier: 2-s2.0-84943316739

(DOI: 10.1039/C5CC01067E, PubMed: 25977944, Elsevier: Scopus) Kohei Sato, Keisuke Kitakaze, Takahiro Nakamura, Naoto Naruse, Keisuke Aihara, Akira Shigenaga, Tsubasa Inokuma, Daisuke Tsuji, Kouji Itou and Akira Otaka :
The total chemical synthesis of the monoglycosylated GM2 ganglioside activator using a novel cysteine surrogate,
Chemical Communications, Vol.51, No.49, 9946-9948, 2015.

(要約): We describe a novel peptide ligation/desulfurization strategy using a -mercapto-N-glycosylated asparagine derivative. The newly developed procedure was successfully applied to the total chemical synthesis of the GM2 ganglioside activator protein bearing a monosaccharide on the native glycosylation site.
(徳島大学機関リポジトリ): ● Metadata: 111882
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/C5CC02967H
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26006093; ● Summary page in Scopus @ Elsevier: 2-s2.0-84931274683

(徳島大学機関リポジトリ: 111882, DOI: 10.1039/C5CC02967H, PubMed: 26006093, Elsevier: Scopus) Keisuke Aihara, Tsubasa Inokuma, Chiaki Komiya, Akira Shigenaga and Akira Otaka :
Synthesis of lactam-bridged cyclic peptides by using olefin metathesis and diimide reduction,
Tetrahedron, Vol.71, No.24, 4183-4191, 2015.

(徳島大学機関リポジトリ): ● Metadata: 111884
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2015.04.093
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-84929702815

(徳島大学機関リポジトリ: 111884, DOI: 10.1016/j.tet.2015.04.093, Elsevier: Scopus) Yusuke Tsuda, Akira Shigenaga, Masaya Denda, Kohei Sato, Keisuke Kitakaze, Takahiro Nakamura, Tsubasa Inokuma, Kouji Itou and Akira Otaka :
Development of chemical methodology for preparation of peptide thioesters applicable to naturally occurring peptides using a sequential quadruple acyl transfer system,
ChemistryOpen, Vol.4, No.4, 448-452, 2015.

(徳島大学機関リポジトリ): ● Metadata: 111883
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/open.201500086
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-84942501459

(徳島大学機関リポジトリ: 111883, DOI: 10.1002/open.201500086, Elsevier: Scopus) Masahiro Furutani, Akihito Uemura, Akira Shigenaga, Chiaki Komiya, Akira Otaka and Kazunori Matsuura :
Inside Back Cover: A photoinduced growth system of peptide nanofibres addressed by DNA hybridization,
Chemical Communications, Vol.51, No.38, 8197, 2015.

(要約): Spatiotemporal control of peptide nanofibre growth was achieved by photocleavage of a DNA-conjugated -sheet forming peptide that is linked through a photoresponsive amino acid residue. Peptide nanofibres were selectively formed by photocleaving the conjugate on a complementary DNA-immobilised glass substrate.
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/C5CC90206A
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1039/C5CC90206A

(DOI: 10.1039/C5CC90206A) Masahiro Furutani, Akihito Uemura, Akira Shigenaga, Chiaki Komiya, Akira Otaka and Kazunori Matsuura :
A photoinduced growth system of peptide nanofibres addressed by DNA hybridization,
Chemical Communications, Vol.51, No.38, 8020-8022, 2015.

(要約): Spatiotemporal control of peptide nanofibre growth was achieved by photocleavage of a DNA-conjugated -sheet forming peptide that is linked through a photoresponsive amino acid residue. Peptide nanofibres were selectively formed by photocleaving the conjugate on a complementary DNA-immobilised glass substrate.
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/c5cc01452b
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25778790; ● Summary page in Scopus @ Elsevier: 2-s2.0-84928803697

(DOI: 10.1039/c5cc01452b, PubMed: 25778790, Elsevier: Scopus) Yuki Haraya, Kento Tanaka, Kohei Tsuji, Yasuo Asami, Hironori Izawa, Akira Shigenaga, Akira Otaka, Hiroyuki Saito and Kohsaku Kawakami :
Molecular Complex Composed of -Cyclodextrin-Grafted Chitosan and pH-Sensitive Amphipathic Peptide for Enhancing Cellular Cholesterol Efflux under Acidic pH,
Bioconjugate Chemistry, Vol.26, No.3, 572-581, 2015.

(要約): Excess of cholesterol in peripheral cells is known to lead to atherosclerosis. In this study, a molecular complex composed of -cyclodextrin-grafted chitosan (BCC) and cellular cholesterol efflux enhancing peptide (CEEP), synthesized by modifying pH sensitive amphipathic GALA peptide, is introduced with the eventual aim of treating atherosclerosis. BCC has a markedly enhanced ability to induce cholesterol efflux from cell membranes compared to -cyclodextrin, and the BCC-CEEP complex exhibited a 2-fold increase in cellular cholesterol efflux compared to BCC alone under weakly acidic conditions. Isothermal titration calorimetry and fluorescence spectroscopy measurements demonstrated that the random coil structure of CEEP at neutral pH converted to the -helical structure at acidic pH, resulting in a three-order larger binding constant to BCC (K = 3.7 × 10(7) at pH 5.5) compared to that at pH 7.4 (K = 7.9 × 10(4)). Such high-affinity binding of CEEP to BCC at acidic pH leads to the formation of 100-nm-sized aggregate with positive surface charge, which would efficiently interact with cell membranes and induce cholesterol efflux. Since the cholesterol efflux ability of HDL is thought to be impaired under acidic environments in advanced atherosclerotic lesions, the BCC-CEEP complex might serve as a novel nanomaterial for treating atherosclerosis.
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/acs.bioconjchem.5b00037
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25705984; ● Summary page in Scopus @ Elsevier: 2-s2.0-84924981137

(DOI: 10.1021/acs.bioconjchem.5b00037, PubMed: 25705984, Elsevier: Scopus) Keisuke Aihara, Chiaki Komiya, Akira Shigenaga, Tsubasa Inokuma, Daisuke Takahashi and Akira Otaka :
Liquid-phase synthesis of bridged peptides using olefin metathesis of protected peptide with long aliphatic chain anchor,
Organic Letters, Vol.17, No.3, 696-699, 2015.

(要約): Bridged peptides including stapled peptides are attractive tools for regulating protein-protein interactions (PPIs). An effective synthetic methodology in a heterogeneous system for the preparation of these peptides using olefin metathesis and hydrogenation of protected peptides with a long aliphatic chain anchor is reported.
(キーワード): Alkenes / Hydrogenation / Molecular Structure / Peptides
(徳島大学機関リポジトリ): ● Metadata: 111891
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/ol503718j
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25629979; ● Summary page in Scopus @ Elsevier: 2-s2.0-84922622683

(徳島大学機関リポジトリ: 111891, DOI: 10.1021/ol503718j, PubMed: 25629979, Elsevier: Scopus) Jun Yamamoto, Nami Maeda, Chiaki Komiya, Tomohiro Tanaka, Masaya Denda, Koji Ebisuno, Wataru Nomura, Hirokazu Tamamura, Youichi Sato, Aiko Yamauchi, Akira Shigenaga and Akira Otaka :
Development of a fluoride-responsive amide bond cleavage device that is potentially applicable to a traceable linker,
Tetrahedron, Vol.70, No.34, 5122-5127, 2014.

(徳島大学機関リポジトリ): ● Metadata: 111908
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2014.05.110
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-84903391352

(徳島大学機関リポジトリ: 111908, DOI: 10.1016/j.tet.2014.05.110, Elsevier: Scopus) Jun Yamamoto, Masaya Denda, Nami Maeda, Miku Kita, Chiaki Komiya, Tomohiro Tanaka, Wataru Nomura, Hirokazu Tamamura, Youichi Sato, Aiko Yamauchi, Akira Shigenaga and Akira Otaka :
Development of a traceable linker containing a thiol-responsive amino acid for the enrichment and selective labelling of target proteins,
Organic & Biomolecular Chemistry, Vol.12, No.23, 3821-3826, 2014.

(要約): A traceable linker that is potentially applicable to identification of a target protein of bioactive compounds was developed. It enabled not only thiol-induced cleavage of the linker for enrichment of the target protein but also selective labelling to pick out the target from contaminated non-target proteins for facile identification.
(キーワード): Amides / Amino Acids / Click Chemistry / Electrophoresis, Polyacrylamide Gel / Peptides / Proteins / Staining and Labeling / Sulfhydryl Compounds
(徳島大学機関リポジトリ): ● Metadata: 111911
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/C4OB00622D
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24806338; ● Summary page in Scopus @ Elsevier: 2-s2.0-84901285801

(徳島大学機関リポジトリ: 111911, DOI: 10.1039/C4OB00622D, PubMed: 24806338, Elsevier: Scopus) Koji Ebisuno, Masaya Denda, Keiji Ogura, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Development of caged non-hydrolyzable phosphoamino acids and application to photo-control of binding affinity of phosphopeptide mimetic to phosphopeptide-recognizing protein,
Bioorganic & Medicinal Chemistry, Vol.22, No.11, 2984-2991, 2014.

(要約): The design and synthesis of caged non-hydrolyzable phospho-serine, -threonine, and -tyrosine derivatives that generate parent non-hydrolyzable phosphoamino acids, containing a difluoromethylene unit instead of the oxygen of a phosphoester, after UV-irradiation are described. The caged non-hydrolyzable amino acids were incorporated into peptides by standard Fmoc solid-phase peptide synthesis, and the obtained peptides were successfully converted to the parent non-hydrolyzable phosphopeptides by UV-irradiation. Application of the caged non-hydrolyzable phosphoserine-containing peptide to photo-control the binding affinity of the peptide to 14-3-3 protein is also reported.
(キーワード): 14-3-3 Proteins / Phosphoamino Acids / Phosphopeptides / Photochemical Processes / Ultraviolet Rays
(徳島大学機関リポジトリ): ● Metadata: 111910
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bmc.2014.04.002
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24768166; ● Summary page in Scopus @ Elsevier: 2-s2.0-84899987488

(徳島大学機関リポジトリ: 111910, DOI: 10.1016/j.bmc.2014.04.002, PubMed: 24768166, Elsevier: Scopus) Takahiro Nakamura, Akira Shigenaga, Kohei Sato, Yusuke Tsuda, Ken Sakamoto and Akira Otaka :
Examination of native chemical ligation using peptidyl prolyl thioester,
Chemical Communications, Vol.50, No.1, 58-60, 2014.

(要約): Peptidyl prolyl thioesters, which have been regarded as too unreactive for practical use in native chemical ligations (NCLs), were proven to be versatile reagents in peptide coupling. Tuning the reactivity of prolyl thioesters enabled a one-pot/sequential NCL reaction based on kinetically controlled ligation.
(キーワード): Amino Acid Sequence / Esters / Kinetics / Molecular Sequence Data / Peptides / Sulfhydryl Compounds
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/C3CC47228K
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24195110; ● Summary page in Scopus @ Elsevier: 2-s2.0-84888622629

(DOI: 10.1039/C3CC47228K, PubMed: 24195110, Elsevier: Scopus) Emi Adachi, Asako Kosaka, Kohei Tsuji, Chiharu Mizuguchi, Hiroyuki Kawashima, Akira Shigenaga, Kohjiro Nagao, Kenichi Akaji, Akira Otaka and Hiroyuki Saito :
The extreme N-terminal region of human apolipoprotein A-I has a strong propensity to form amyloid fibrils.,
FEBS Letters, Vol.588, No.3, 389-394, 2013.

(要約): The N-terminal 1-83 residues of apolipoprotein A-I (apoA-I) have a strong propensity to form amyloid fibrils, in which the 46-59 segment was reported to aggregate to form amyloid-like fibrils. In this study, we demonstrated that a fragment peptide comprising the extreme N-terminal 1-43 residues strongly forms amyloid fibrils with a transition to -sheet-rich structure, and that the G26R point mutation enhances the fibril formation of this segment. Our results suggest that in addition to the 46-59 segment, the extreme N-terminal region plays a crucial role in the development of amyloid fibrils by the N-terminal fragment of amyloidogenic apoA-I variants.
(キーワード): Amyloid / Apolipoprotein A-I / Circular Dichroism / Humans / Microscopy, Atomic Force / Peptide Fragments / Point Mutation / Protein Conformation / Protein Structure, Secondary / Spectroscopy, Fourier Transform Infrared
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.febslet.2013.11.031
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24316228; ● Search Scopus @ Elsevier (PMID): 24316228; ● Search Scopus @ Elsevier (DOI): 10.1016/j.febslet.2013.11.031

(DOI: 10.1016/j.febslet.2013.11.031, PubMed: 24316228) Kosuke Tanegashima, Kohei Tsuji, Kenji Suzuki, Akira Shigenaga, Akira Otaka and Takahiko Hara :
Dimeric peptides of the C-terminal region of CXCL14 function as CXCL12 inhibitors,
FEBS Letters, Vol.587, No.23, 3770-3775, 2013.

(要約): We recently reported that CXCL14 binds to CXCR4 with high affinity and inhibits CXCL12-mediated chemotaxis. Here we found that the C-terminal 51-77 amino acid residues of CXCL14 are responsible for CXCR4 binding. A disulfide dimer peptide of CXCL14(51-77) bound to CXCR4 with comparable affinity to full length CXCL14, and exhibited CXCL12 inhibitor activity. CXCR4 was efficiently internalized upon binding of dimeric CXCL14(51-77), thereby being reduced on the cell surface. Substitution of 5 amino acid residues in combination with the use of an oxime linker for dimerization increased the solubility and chemical stability of the dimeric CXCL14(51-77).
(キーワード): Cell Line, Tumor / Cell Membrane / Chemokine CXCL12 / Chemokines, CXC / Dimerization / Disulfides / Humans / Mutation / Peptides / Protein Binding / Protein Multimerization / Protein Stability / Protein Structure, Tertiary / Protein Transport
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.febslet.2013.10.017
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24161674; ● Summary page in Scopus @ Elsevier: 2-s2.0-84888014682

(DOI: 10.1016/j.febslet.2013.10.017, PubMed: 24161674, Elsevier: Scopus) Kohei Sato, Akira Shigenaga, Keisuke Kitakaze, Ken Sakamoto, Daisuke Tsuji, Kouji Itou and Akira Otaka :
Chemical synthesis of biologically active monoglycosylated GM2-activator protein analog using N-sulfanylethylanilide peptide,
Angewandte Chemie International Edition, Vol.52, No.30, 7855-7859, 2013.

(要約): Going to SEA(lide): Total chemical synthesis of a 162-residue glycoprotein analogue of the monoglycosylated human GM2-activator protein (GM2AP) was achieved. Key steps were the use of N-sulfanylethylanilide (SEAlide) peptides in the kinetic chemical ligation synthesis of a large peptide fragment, and a convergent native chemical ligation for final fragment assembly.
(キーワード): Amino Acid Sequence / Anilides / G(M2) Activator Protein / G(M2) Ganglioside / Glycosylation / Humans / Kinetics / Molecular Sequence Data / Peptide Fragments / Sulfhydryl Compounds
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/anie.201303390
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23765733; ● Summary page in Scopus @ Elsevier: 2-s2.0-84880361310

(DOI: 10.1002/anie.201303390, PubMed: 23765733, Elsevier: Scopus) Kosuke Tanegashima, Kenji Suzuki, Yuki Nakayama, Kohei Tsuji, Akira Shigenaga, Akira Otaka and Takahiko Hara :
CXCL14 is a natural inhibitor of the CXCL12-CXCR4 signaling axis,
FEBS Letters, Vol.587, No.12, 1731-1735, 2013.

(要約): Activation of the CXCL12-CXCR4 pathway is crucial for the migration of hematopoietic stem cells, various immune cells, and malignant tumor cells. Here, we show that another CXC chemokine, CXCL14, specifically binds to CXCR4 with high affinity and inhibits the CXCL12-mediated chemotaxis of human leukemia-derived cell lines and CD34(+) hematopoietic progenitor cells. Thus, CXCL14 functions as a natural inhibitor of CXCL12. Our observations suggest that CXCL14 represents, along with CXCR7, molecules that co-evolved with the CXCL12-CXCR4 axis to modulate important physiological processes in development, stem cell maintenance, and immune responses.
(キーワード): Bone Marrow Cells / Cell Line, Tumor / Chemokine CXCL12 / Chemokines, CXC / Chemotaxis / Hematopoietic Stem Cells / Humans / Receptors, CXCR / Receptors, CXCR4 / Signal Transduction / Substrate Specificity
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.febslet.2013.04.046
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23669361; ● Search Scopus @ Elsevier (PMID): 23669361; ● Search Scopus @ Elsevier (DOI): 10.1016/j.febslet.2013.04.046

(DOI: 10.1016/j.febslet.2013.04.046, PubMed: 23669361) Ken Sakamoto, Kohei Sato, Akira Shigenaga, Kohei Tsuji, Shugo Tsuda, Hajime Hibino, Yuji Nishiuchi and Akira Otaka :
Synthetic procedure for N-Fmoc amino acyl-N-sulfanylethylaniline linker as crypto-peptide thioester precursor with application to native chemical ligation,
The Journal of Organic Chemistry, Vol.77, No.16, 6948-6958, 2012.

(要約): N-sulfanylethylanilide (SEAlide) peptides 1, obtainable using Fmoc-based solid-phase peptide synthesis (Fmoc SPPS), function as crypto-thioesters in native chemical ligation (NCL), yielding a wide variety of peptides/proteins. Their acylating potential with N-terminal cysteinyl peptides 2 can be tuned by the presence or absence of phosphate salts, leading to one-pot/multifragment ligation, operating under kinetically controlled conditions. SEAlide peptides have already been shown to be promising for use in protein synthesis; however, a widely applicable method for the synthesis of N-Fmoc amino acyl-N-sulfanylethylaniline linkers 4, required for the preparation of SEAlide peptides, is unavailable. The present study addresses the development of efficient condensation protocols of 20 naturally occurring amino acid derivatives to the N-sulfanylethylaniline linker 5. N-Fmoc amino acyl aniline linkers 4 of practical use in NCL chemistry, except in the case of the proline- or aspartic acid-containing linker, were successfully synthesized by coupling of POCl(3)- or SOCl(2)-activated Fmoc amino acid derivatives with sodium anilide species 6, without accompanying racemization and loss of side-chain protection. Furthermore, SEAlide peptides 7 possessing various C-terminal amino acids (Gly, His, Phe, Ala, Asn, Ser, Glu, and Val) were shown to be of practical use in NCL chemistry.
(キーワード): Acylation / Amino Acids / Anilides / Esters / Fluorenes / Kinetics / Peptides / Phosphates / Solid-Phase Synthesis Techniques / Sulfhydryl Compounds / Sulfur Compounds
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jo3011107
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22816612; ● Search Scopus @ Elsevier (PMID): 22816612; ● Search Scopus @ Elsevier (DOI): 10.1021/jo3011107

(DOI: 10.1021/jo3011107, PubMed: 22816612) Keiji Ogura, Akira Shigenaga, Koji Ebisuno, Hiroko Hirakawa and Akira Otaka :
Fmoc-based solid phase synthesis of adenylylated peptides using diester-type adenylylated amino acid derivatives,
Tetrahedron Letters, Vol.53, No.27, 3429-3432, 2012.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tetlet.2012.04.063
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tetlet.2012.04.063

(DOI: 10.1016/j.tetlet.2012.04.063) Akira Shigenaga, Keiji Ogura, Hiroko Hirakawa, Jun Yamamoto, Koji Ebisuno, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Akira Otaka :
Development of a reduction-responsive amino acid that induces peptide bond cleavage in hypoxic cells,
ChemBioChem, Vol.13, 968-971, 2012.

(要約): Hypoxia-responsive amino acids are indispensable in the preparation of hypoxic tumor-specific peptidyl prodrugs. In this paper, the design and synthesis of a reduction-responsive amino acid that induces peptide bond cleavage after reduction of the nitro group are described. Application to hypoxia-responsive peptide bond cleavage system is also reported.
(キーワード): Amides / Amino Acids / Cell Hypoxia / Fluorescence Resonance Energy Transfer / Molecular Structure / Oxidation-Reduction / Peptides / Prodrugs
(徳島大学機関リポジトリ): ● Metadata: 111913
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cbic.201200141
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22505188; ● Search Scopus @ Elsevier (PMID): 22505188; ● Search Scopus @ Elsevier (DOI): 10.1002/cbic.201200141

(徳島大学機関リポジトリ: 111913, DOI: 10.1002/cbic.201200141, PubMed: 22505188) Hao Ding, Akira Shigenaga, Kohei Sato, Ko Morishita and Akira Otaka :
Dual kinetically-controlled native chemical ligation using a combination of sulfanylproline and sulfanylethylanilide peptide,
Organic Letters, Vol.13, No.20, 5588-5591, 2011.

(要約): Dual kinetically controlled native chemical ligation using a newly developed sulfanylproline-mediated reaction in combination with an N-sulfanylethylanilide peptide was successfully applied to a previously unreported sequential coupling of peptide fragments added simultaneously to the reaction.
(キーワード): Amino Acid Sequence / Kinetics / Molecular Structure / Neuropeptides / Peptides / Stereoisomerism / Sulfhydryl Compounds
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/ol202316v
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21916452; ● Search Scopus @ Elsevier (PMID): 21916452; ● Search Scopus @ Elsevier (DOI): 10.1021/ol202316v

(DOI: 10.1021/ol202316v, PubMed: 21916452) Akira Shigenaga, Ko Morishita, Keiko Yamaguchi, Hao Ding, Koji Ebisuno, Kohei Sato, Jun Yamamoto, Kenichi Akaji and Akira Otaka :
Development of UV-responsive catch-and-release system of a cysteine protease model peptide,
Tetrahedron, Vol.67, No.46, 8879-8886, 2011.

(徳島大学機関リポジトリ): ● Metadata: 111905
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2011.09.062
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tet.2011.09.062

(徳島大学機関リポジトリ: 111905, DOI: 10.1016/j.tet.2011.09.062) Kohei Sato, Akira Shigenaga, Kohei Tsuji, Shugo Tsuda, Yoshitake Sumikawa, Ken Sakamoto and Akira Otaka :
N-Sulfanylethylanilide Peptide as a Crypto-Thioester Peptide,
ChemBioChem, Vol.12, No.12, 1840-1844, 2011.

(キーワード): Acylation / Amino Acid Sequence / Anilides / Chromatography, High Pressure Liquid / Combinatorial Chemistry Techniques / Kinetics / Molecular Sequence Data / Peptides / Sulfides
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cbic.201100241
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21739560; ● Search Scopus @ Elsevier (PMID): 21739560; ● Search Scopus @ Elsevier (DOI): 10.1002/cbic.201100241

(DOI: 10.1002/cbic.201100241, PubMed: 21739560) Kohei Tsuji, Akira Shigenaga, Yoshitake Sumikawa, Kosuke Tanegashima, Kohei Sato, Keisuke Aihara, Takahiko Hara and Akira Otaka :
Application of N-C- or C-N-directed sequential native chemical ligation to the preparation of CXCL14 analogs and their biological evaluation,
Bioorganic & Medicinal Chemistry, Vol.19, No.13, 4014-4020, 2011.

(要約): CXCL14 is a chemokine that exhibits chemoattractant activity for activated macrophages, immature dendric cells, natural killer cells, and epithelial tumor cells. Its potential role as a metabolic regulator has recently been disclosed. However, a complete understanding of its physiological roles remains elusive. This is partly due to the lack of appropriate CXCL14-based molecular probes to explore the biological functions of CXCL14. In this context, we have developed synthetic protocols that provide access to a wide variety of CXCL14 analogs. Two sequential native chemical ligation (NCL) protocols, which proceed in opposite directions, have been used to assemble CXCL14 analogs from peptide fragments. The first involved a conventional C-N-directed sequential NCL, and afforded wild-type CXCL14. The other used peptide thioacids in N-C-directed elongation, and yielded CXCL14 analogs with molecular diversity at the C-terminal fragment. The CXCL14 analogs prepared showed biological activity on human monocytic leukemia-derived THP-1 cells that was comparable to that of wild-type CXCL14.
(キーワード): Amino Acid Sequence / Carbon / Cell Line, Tumor / Chemokines, CXC / Humans / Molecular Sequence Data / Nitrogen / Peptides
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bmc.2011.05.018
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21658958; ● Search Scopus @ Elsevier (PMID): 21658958; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2011.05.018

(DOI: 10.1016/j.bmc.2011.05.018, PubMed: 21658958) Akira Shigenaga, Hiroko Hirakawa, Jun Yamamoto, Keiji Ogura, Masaya Denda, Keiko Yamaguchi, Daisuke Tsuji, Kouji Itou and Akira Otaka :
Design and synthesis of caged ceramide: UV-responsive ceramide releasing system based on UV-induced amide bond cleavage followed by O-N acyl transfer,
Tetrahedron, Vol.67, No.22, 3984-3990, 2011.

(徳島大学機関リポジトリ): ● Metadata: 111907
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2011.04.048
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tet.2011.04.048

(徳島大学機関リポジトリ: 111907, DOI: 10.1016/j.tet.2011.04.048) Akira Shigenaga, Jun Yamamoto, Naomi Nishioka and Akira Otaka :
Enantioselective synthesis of stimulus-responsive amino acid via asymmetric -amination of aldehyde,
Tetrahedron, Vol.66, No.37, 7367-7372, 2010.

(徳島大学機関リポジトリ): ● Metadata: 111904
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2010.07.033
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tet.2010.07.033

(徳島大学機関リポジトリ: 111904, DOI: 10.1016/j.tet.2010.07.033) Yoshimi Nishikawa, Yoshifumi Takahara, Shinichi Asada, Akira Shigenaga, Akira Otaka, Kouki Kitagawa and Takaki Koide :
A structure activity relationship study elucidating the mechanism of sequence-specific collagen recognition by the chaperone HSP47,
Bioorganic & Medicinal Chemistry, Vol.18, No.11, 3767-3775, 2010.

(要約): Heat-shock protein 47 (HSP47) is a chaperone that facilitates the proper folding of procollagen. Our previous studies showed that the high-affinity HSP47-binding motif in the collagen triple helix is Xaa-(Thr/Pro)-Gly-Xaa-Arg-Gly. In this study, we further investigated structural requirements for the HSP47-binding motif, using synthetic triple-helical collagen-model peptides with systematic amino acid substitutions at either the Thr/Pro (=Yaa(-3)) or the Arg (=Yaa(0)) position. Results obtained from in vitro binding assays indicated that HSP47 detects the side-chain structure of Arg at the Yaa(0)-position, while the Yaa(-3) amino acid serves as the secondary recognition site that affects affinity to HSP47.
(キーワード): Amino Acid Sequence / Animals / Binding Sites / Collagen / HSP47 Heat-Shock Proteins / Mice / Protein Binding / Structure-Activity Relationship
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bmc.2010.04.054
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20471275; ● Search Scopus @ Elsevier (PMID): 20471275; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2010.04.054

(DOI: 10.1016/j.bmc.2010.04.054, PubMed: 20471275) Akira Shigenaga, Jun Yamamoto, Yoshitake Sumikawa, Toshiaki Furuta and Akira Otaka :
Development and photo-responsive peptide bond cleavage reaction of two-photon near-infrared excitation responsive peptide,
Tetrahedron Letters, Vol.51, No.21, 2868-2871, 2010.

(徳島大学機関リポジトリ): ● Metadata: 111903
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tetlet.2010.03.079
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tetlet.2010.03.079

(徳島大学機関リポジトリ: 111903, DOI: 10.1016/j.tetlet.2010.03.079) Akira Shigenaga, Yoshitake Sumikawa, Shugo Tsuda, Kohei Sato and Akira Otaka :
Sequential native chemical ligation utilizing peptide thioacids derived from newly developed Fmoc-based synthetic method,
Tetrahedron, Vol.66, No.18, 3290-3296, 2010.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2010.03.016
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tet.2010.03.016

(DOI: 10.1016/j.tet.2010.03.016) Akira Shigenaga, Jun Yamamoto, Hiroko Hirakawa, Keiji Ogura, Ko Morishita, Nami Maeda and Akira Otaka :
Development of thiol-responsive amide bond cleavage device and its application for peptide nucleic acid-based DNA releasing system,
Tetrahedron Letters, Vol.51, No.18, 2525-2528, 2010.

(徳島大学機関リポジトリ): ● Metadata: 111901
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tetlet.2010.03.006
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tetlet.2010.03.006

(徳島大学機関リポジトリ: 111901, DOI: 10.1016/j.tetlet.2010.03.006) Yoshito Fujimoto, Takuma Shiraki, Yuji Horiuchi, Tsuyoshi Waku, Akira Shigenaga, Akira Otaka, Tsuyoshi Ikura, Kazuhiko Igarashi, Saburo Aimoto, Shin-ichi Take and Kosuke Morikawa :
Proline cis/trans isomerase Pin1 regulates peroxisome proliferators-activated receptor g activity through the direct binding to the AF-1 domain,
The Journal of Biological Chemistry, Vol.285, No.5, 3126-3132, 2010.

(要約): The important roles of a nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) are widely accepted in various biological processes as well as metabolic diseases. Despite the worldwide quest for pharmaceutical manipulation of PPARgamma activity through the ligand-binding domain, very little information about the activation mechanism of the N-terminal activation function-1 (AF-1) domain. Here, we demonstrate the molecular and structural basis of the phosphorylation-dependent regulation of PPARgamma activity by a peptidyl-prolyl isomerase, Pin1. Pin1 interacts with the phosphorylated AF-1 domain, thereby inhibiting the polyubiquitination of PPARgamma. The interaction and inhibition are dependent upon the WW domain of Pin1 but are independent of peptidyl-prolyl cis/trans-isomerase activity. Gene knockdown experiments revealed that Pin1 inhibits the PPARgamma-dependent gene expression in THP-1 macrophage-like cells. Thus, our results suggest that Pin1 regulates macrophage function through the direct binding to the phosphorylated AF-1 domain of PPARgamma.
(キーワード): Animals / Cell Line / Humans / Macrophages / Magnetic Resonance Spectroscopy / Mice / Mutation / PPAR gamma / Peptidylprolyl Isomerase / Phosphorylation / Proline / Protein Binding / Protein Structure, Tertiary / Recombinant Proteins / Surface Plasmon Resonance
(出版サイトへのリンク): ● Publication site (DOI): 10.1074/jbc.M109.055095
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19996102; ● Search Scopus @ Elsevier (PMID): 19996102; ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M109.055095

(DOI: 10.1074/jbc.M109.055095, PubMed: 19996102) S.-M Yun, T Moulaei, D Lim, J.K Bang, J.-E Park, S.R Shenoy, F Liu, Y.H Kang, C Liao, N.-K Soung, S Lee, D.-Y Yoon, Y Lim, D.-H Lee, Akira Otaka, E Appella, J.B McMahon, M.C Nicklaus, T.R.Jr. Burke, M.B Yaffe, A Wlodawer and K.S Lee :
Structural and functional analyses of minimal phosphopeptides targeting the polo-box domain of polo-like kinase 1,
Nature Structural & Molecular Biology, Vol.16, No.8, 876-882, 2009.

(要約): Polo-like kinase-1 (Plk1) has a pivotal role in cell proliferation and is considered a potential target for anticancer therapy. The noncatalytic polo-box domain (PBD) of Plk1 forms a phosphoepitope binding module for protein-protein interaction. Here, we report the identification of minimal phosphopeptides that specifically interact with the PBD of human PLK1, but not those of the closely related PLK2 and PLK3. Comparative binding studies and analyses of crystal structures of the PLK1 PBD in complex with the minimal phosphopeptides revealed that the C-terminal SpT dipeptide functions as a high-affinity anchor, whereas the N-terminal residues are crucial for providing specificity and affinity to the interaction. Inhibition of the PLK1 PBD by phosphothreonine mimetic peptides was sufficient to induce mitotic arrest and apoptotic cell death. The mode of interaction between the minimal peptide and PBD may provide a template for designing therapeutic agents that target PLK1.
(キーワード): Amino Acid Sequence / Binding Sites / Binding, Competitive / Cell Cycle Proteins / HeLa Cells / Humans / Immunoblotting / Models, Molecular / Molecular Sequence Data / Phosphopeptides / Phosphorylation / Protein Binding / Protein Structure, Tertiary / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins / Thermodynamics / Threonine
(出版サイトへのリンク): ● Publication site (DOI): 10.1038/nsmb.1628
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19597481; ● Search Scopus @ Elsevier (PMID): 19597481; ● Search Scopus @ Elsevier (DOI): 10.1038/nsmb.1628

(DOI: 10.1038/nsmb.1628, PubMed: 19597481) Yoko Yamaki, Akira Shigenaga, Jinglan Li, Yasuyuki Shimohigashi and Akira Otaka :
Synthesis of amide-type fluoroalkene dipeptide isosteres by an intramolecular redox reaction,
The Journal of Organic Chemistry, Vol.74, No.9, 3278-3285, 2009.

(要約): We previously achieved NHC-mediated preparation of ester-type fluoroalkene dipeptide isosteres (ES-FADIs, 4) by an intramolecular redox reaction. In the present study, a cyanide ion-mediated reaction was successfully applied to the conversions of gamma,gamma-difluoro-alpha,beta-enoylsilane 1 or 2 to amide-type fluoroalkene isosteres (AM-FADIs, 5 or 6). The use of catalytic cyanide ion allowed synthesis of chiral auxiliary incorporated FADI 15b which was then subjected to a diastereoselective alpha-alkylation reaction to yield alpha-substituted FADIs 17. Furthermore, the presented amidation protocol was used for straightforward incorporation of FADI into peptidyl resin.
(キーワード): Alkenes / Alkylation / Amides / Cyanides / Dipeptides / Oxidation-Reduction / Stereoisomerism / Substrate Specificity
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jo900135t
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19331368; ● Search Scopus @ Elsevier (PMID): 19331368; ● Search Scopus @ Elsevier (DOI): 10.1021/jo900135t

(DOI: 10.1021/jo900135t, PubMed: 19331368) Yoko Yamaki, Akira Shigenaga, Kenji Tomita, Tetsuo Narumi, Nobutaka Fujii and Akira Otaka :
Synthesis of fluoroalkene dipeptide isosteres by an intramolecular redox reaction utilizing N-heterocyclic carbenes (NHCs),
The Journal of Organic Chemistry, Vol.74, No.9, 3272-3277, 2009.

(要約): (Z)-Fluoroalkene dipeptide isosteres (FADIs 16) have served as potential dipeptide mimetics possessing the substitution of fluoroalkenes for parent peptide bonds. Previously, we synthesized FADIs by reduction of gamma,gamma-difluoro-alpha,beta-enoates with organocoppers or SmI(2), which prompted us to use an intramolecular redox reaction mediated by N-heterocyclic carbenes (NHCs) for the preparation of FADIs. Instead of the enoates, gamma,gamma-difluoro-alpha,beta-enal 20 and gamma,gamma-difluoro-alpha,beta-enoylsilane 34 were converted to FADIs by an NHC-mediated intramolecular redox reaction, whereby aldehyde components reduced the allylic difluoride component in an S(N)2' manner with accompanying monodefluorination.
(キーワード): Alkenes / Biomimetics / Dipeptides / Heterocyclic Compounds / Methane / Oxidation-Reduction / Silanes
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jo900134k
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19331367; ● Search Scopus @ Elsevier (PMID): 19331367; ● Search Scopus @ Elsevier (DOI): 10.1021/jo900134k

(DOI: 10.1021/jo900134k, PubMed: 19331367) Shugo Tsuda, Akira Shigenaga, Kiyomi Bando and Akira Otaka :
N→S acyl-transfer-mediated synthesis of peptide thioesters using anilide derivatives,
Organic Letters, Vol.11, No.4, 823-826, 2009.

(要約): N-->S acyl-transfer-mediated synthesis of peptide thioesters utilizing an N-aminoacyl-N-sulfanylethylaminobenzoic acid derivative has been examined. The developed synthetic methodology for peptide thioesters is compatible with Fmoc solid-phase peptide synthesis (SPPS).
(キーワード): Anilides / Esters / Molecular Structure / Nitrogen / Peptides / Sulfur
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/ol8028093
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19161341; ● Search Scopus @ Elsevier (PMID): 19161341; ● Search Scopus @ Elsevier (DOI): 10.1021/ol8028093

(DOI: 10.1021/ol8028093, PubMed: 19161341) Akira Shigenaga, Jun Yamamoto, Hiroko Hirakawa, Keiko Yamaguchi and Akira Otaka :
FRET-based assay of the processing reaction kinetics of stimulus-responsive peptides: Influence of amino acid sequence on reaction kinetics,
Tetrahedron, Vol.65, No.11, 2212-2216, 2009.

(徳島大学機関リポジトリ): ● Metadata: 111902
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2009.01.063
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tet.2009.01.063

(徳島大学機関リポジトリ: 111902, DOI: 10.1016/j.tet.2009.01.063) H Nishikawa, S Nakamura, E Kodama, S Ito, K Kajiwara, K Izumi, Y Sakagami, S Oishi, T Ohkubo, Y Kobayashi, Akira Otaka, N Fujii and M Matsuoka :
Electrostatically constrained alpha-helical peptide inhibits replication of HIV-1 resistant to Enfuvirtide,
The International Journal of Biochemistry & Cell Biology, Vol.41, No.4, 891-899, 2009.

(要約): Alpha-helical peptides, such as T-20 (enfuvirtide) and C34, derived from the gp41 carboxyl-terminal heptad repeat (C-HR) of HIV-1, inhibit membrane fusion of HIV-1 and the target cells. Although T-20 effectively suppresses the replication of multi-drug resistant HIV variants both in vitro and in vivo, prolonged therapy with T-20 induces emergence of T-20 resistant variants. In order to suppress the emergence of such resistant variants, we introduced charged and hydrophilic amino acids, glutamic acid (E) and lysine (K), at the solvent accessible site of C34. In particular, the modified peptide, SC34EK, demonstrates remarkably potent inhibition of membrane fusion by the resistant HIV-1 variants as well as wild-type viruses. The activity was specific to HIV-1 and little influenced by serum components. We found a strong correlation between the anti-HIV-1 activities of these peptides and the thermostabilities of the 6-helix bundles that are formed with these peptides. We also obtained the crystal structure of SC34EK in complex with a 36 amino acid sequence (N36) comprising the amino-terminal heptad repeat of HIV-1. The EK substitutions in the sequence of SC34EK were directed toward the solvent and generated an electrostatic potential, which may result in enhanced alpha-helicity of the peptide inhibitor. The 6-helix bundle complex of SC34EK with N36 appears to be structurally similar to that of C34 and N36. Our approach to enhancing alpha-helicity of the peptide inhibitor may enable future design of highly effective and specific HIV-1 inhibitors.
(キーワード): Amino Acid Sequence / Animals / Cattle / Circular Dichroism / Drug Design / Drug Resistance, Viral / HIV Envelope Protein gp41 / HIV Fusion Inhibitors / HIV-1 / HeLa Cells / Humans / Molecular Sequence Data / Peptide Fragments / Peptides / Protein Binding / Protein Structure, Secondary / Static Electricity / Structure-Activity Relationship / Virus Replication
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.biocel.2008.08.039
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18834950; ● Search Scopus @ Elsevier (PMID): 18834950; ● Search Scopus @ Elsevier (DOI): 10.1016/j.biocel.2008.08.039

(DOI: 10.1016/j.biocel.2008.08.039, PubMed: 18834950) H. Nishikawa, S. Oishi, M. Fujita, K. Watanabe, R. Tokiwa, H. Ohno, E. Kodama, K. Izumi, K. Kajiwara, T. Naitoh, M. Matsuoka, Akira Otaka and N. Fujii :
Identification of minimal sequence for HIV-1 fusion inhibitors,
Bioorganic & Medicinal Chemistry, Vol.16, No.20, 9184-9187, 2008.

(要約): Emergence of multi-drug resistant HIV-1 is a serious problem for AIDS treatment. Recently, the virus-cell membrane fusion process has been identified as a promising target for the development of novel drugs against these resistant variants. In this study, we identified a 29-residue peptide fusion inhibitor, SC29EK, which shows activity comparable to the previously reported inhibitor SC35EK. Some residues in SC29EK not required for interaction with virus gp41 heptad repeat 1 (HR1) were replaced with a non-proteinogenic amino acid, 2-aminoisobutyric acid (Aib), to stabilize the alpha-helix structure and to provide resistance to peptidases.
(キーワード): Amino Acid Sequence / Animals / Cattle / Circular Dichroism / Drug Design / Drug Resistance, Viral / HIV Envelope Protein gp41 / HIV Fusion Inhibitors / HIV-1 / HeLa Cells / Humans / Molecular Sequence Data / Peptide Fragments / Peptides / Protein Binding / Protein Structure, Secondary / Static Electricity / Structure-Activity Relationship / Virus Replication
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bmc.2008.09.018
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18819810; ● Search Scopus @ Elsevier (PMID): 18819810; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2008.09.018

(DOI: 10.1016/j.bmc.2008.09.018, PubMed: 18819810) Ujike Makoto, Nishikawa Hiroki, Akira Otaka, Yamamoto Naoki, Yamamoto Norio, Matsuoka Masao, Kodama Eiichi, Fujii Nobutaka and Taguchi Fumihiro :
Heptad Repeat-Derived Peptides Block Protease-Mediated Direct Entry from the Cell Surface of Severe Acute Respiratory Syndrome Coronavirus but Not Entry via the Endosomal Pathway,
Journal of Virology, Vol.82, No.1, 588-592, 2008.

(要約): The peptides derived from the heptad repeat (HRP) of severe acute respiratory syndrome coronavirus (SCoV) spike protein (sHRPs) are known to inhibit SCoV infection, yet their efficacies are fairly low. Recently our research showed that some proteases facilitated SCoV's direct entry from the cell surface, resulting in a more efficient infection than the previously known infection via endosomal entry. To compare the inhibitory effect of the sHRP in each pathway, we selected two sHRPs, which showed a strong inhibitory effect on the interaction of two heptad repeats in a rapid and virus-free in vitro assay system. We found that they efficiently inhibited SCoV infection of the protease-mediated cell surface pathway but had little effect on the endosomal pathway. This finding suggests that sHRPs may effectively prevent infection in the lungs, where SCoV infection could be enhanced by proteases produced in this organ. This is the first observation that HRP exhibits different effects on virus that takes the endosomal pathway and virus that enters directly from the cell surface.
(キーワード): Animals / Antiviral Agents / Cercopithecus aethiops / Endosomes / Peptide Hydrolases / Peptides / SARS Virus / Vero Cells / Viral Proteins / Virus Internalization
(出版サイトへのリンク): ● Publication site (DOI): 10.1128/JVI.01697-07
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17942557; ● Search Scopus @ Elsevier (PMID): 17942557; ● Search Scopus @ Elsevier (DOI): 10.1128/JVI.01697-07

(DOI: 10.1128/JVI.01697-07, PubMed: 17942557) Akira Shigenaga, Daisuke Tsuji, Naomi Nishioka, Shugo Tsuda, Kouji Itou and Akira Otaka :
Synthesis of a stimulus-responsive processing device and its application to a nucleocytoplasmic shuttle peptide,
ChemBioChem, Vol.8, No.16, 1929-1931, 2007.

(キーワード): Active Transport, Cell Nucleus / Amino Acids / Animals / CHO Cells / Cell Nucleus / Cricetinae / Cricetulus / Fluorescent Dyes / Molecular Structure / Peptides / Receptors, Cytoplasmic and Nuclear / Ultraviolet Rays
(徳島大学機関リポジトリ): ● Metadata: 111899
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cbic.200700442
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17899557; ● Search Scopus @ Elsevier (PMID): 17899557; ● Search Scopus @ Elsevier (DOI): 10.1002/cbic.200700442

(徳島大学機関リポジトリ: 111899, DOI: 10.1002/cbic.200700442, PubMed: 17899557) Yoshikazu Sasaki, Keiko Yamaguchi, Takashi Tsuji, Akira Shigenaga, Nobutaka Fujii and Akira Otaka :
Development of copper-mediated allylation of c-activated-a,b-unsaturated lactam toward peptide mimetic synthesis,
Tetrahedron Letters, Vol.48, No.18, 3221-3224, 2007.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tetlet.2007.03.017
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tetlet.2007.03.017

(DOI: 10.1016/j.tetlet.2007.03.017) Y. Sasaki, Akira Shigenaga, N. Fujii and Akira Otaka :
Synthesis of (Z)-alkene-containing cis-proline dipeptide mimetics using samarium(II) diiodide (SmI2)-mediated reductive alkylation reaction.,
Tetrahedron, Vol.63, No.9, 2000-2008, 2007.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2006.12.055
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tet.2006.12.055

(DOI: 10.1016/j.tet.2006.12.055) Tesuo Narumi, Ayumu Niida, Kenji Tomita, Shinya Oishi, Akira Otaka, Hiroaki Ohono and Nobutaka Fujii :
A novel one-pot reaction involving organocopper-mediated reduction/transmetalation/asymmetric alkylation, leading to the diastereoselective synthesis of functionalized (Z)-fluoroalkene dipeptide isosteres.,
Chemical Communications, No.45, 4720-4722, 2006.

(要約): By a novel one-pot reaction sequence involving consecutive organocopper-mediated reduction, transmetalation and asymmetric alkylation, a highly diastereoselective synthesis of functionalized (Z)-fluoroalkene dipeptide isosteres was achieved in good to excellent yields.
(キーワード): Alkenes / Alkylation / Copper / Dipeptides / Fluorine / Molecular Structure / Oxidation-Reduction / Stereoisomerism
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/b608596b
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17109048; ● Search Scopus @ Elsevier (PMID): 17109048; ● Search Scopus @ Elsevier (DOI): 10.1039/b608596b

(DOI: 10.1039/b608596b, PubMed: 17109048) Yoshikazu Sasaki, Ayumu Niida, Takashi Tsuji, Akira Shigenaga, Nobutaka Fujii and Akira Otaka :
Stereoselective Synthesis of (Z)-alkene-containing proline dipeptide mimetics,
The Journal of Organic Chemistry, Vol.71, No.13, 4969-4979, 2006.

(要約): In peptides and proteins, the peptide bond between an amino acid and proline exists as an equilibrium mixture of the cis-imide and trans-imide due to the low energy barrier in their interconversion. This feature greatly influences the structure and function of the proline-containing peptides and proteins. Therefore, restricting the amide bond with an (E)- or (Z)-alkene should provide a promising method for elucidating the structure-activity relationships of the peptide and the proteins. In this report, the regio- and stereoselective synthesis of cis-alanylproline (Ala-Pro) type (Z)-alkene dipeptide mimetic is described. The key steps of this synthesis are to introduce a C3 unit onto a gamma-phosphoryloxy-alpha,beta-unsaturated-delta-lactam with an organocopper-mediated anti-S(N)2' reaction and subsequently construct a five-membered proline-like cyclic structure with an intramolecular Suzuki coupling reaction. Hydrolysis of the amide bond in the resulting bicyclic lactam yields the desired cis-Ala-Pro type (Z)-alkene dipeptide isostere. The presented synthetic methodology should be applicable to the general syntheses of other cis-aminoacylproline type (Z)-alkene dipeptide mimetics.
(キーワード): Alkenes / Combinatorial Chemistry Techniques / Dipeptides / Molecular Conformation / Proline / Stereoisomerism
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jo0606002
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16776529; ● Search Scopus @ Elsevier (PMID): 16776529; ● Search Scopus @ Elsevier (DOI): 10.1021/jo0606002

(DOI: 10.1021/jo0606002, PubMed: 16776529) Ayumu Niida, Makiko Mizumoto, Tetsuo Narumi, Eriko Inokuchi, Shinya Oishi, Hiroaki Ohono, Akira Otaka, Kazuo Kitaura and Fujii Nobutaka :
Synthesis of (Z)-Alkene and (E)-Fluoroalkene-Containing Diketopiperazine Mimetics Utilizing Oraganocopper-Mediated Reduction-Alkylation and Diastereoselectivity Examination Using DFT Calculations.,
The Journal of Organic Chemistry, Vol.71, No.11, 4118-4129, 2006.

(要約): We have carefully examined the organocopper-mediated reduction-alkylation of gamma-acetoxy or gamma,gamma-difluoro-alpha,beta-unsaturated-delta-lactams for the synthesis of (Z)-alkene- or (E)-fluoroalkene-containing diketopiperazine mimetics. Reduction of acetates 2, 12, 14, and difluorolactam 18 with higher-order cuprate reagents (Me3CuLi2 x LiI x 3 LiBr), followed by trapping the resulting metal dienolate with an electrophile in a one-pot procedure gave alpha-alkylated-beta,gamma-unsaturated-delta-lactams in good yields. Because of side-chain steric repulsion, we found that alkylation using relatively large electrophiles such as BnBr gave mostly 3,6-trans isomers by kinetic trapping of metal enolates. On the other hand, MeI-mediated alkylations predominantly provided the unexpected 3,6-cis isomers despite the presence of a bulky benzyl side chain. Based on density functional theory calculations, we concluded that formation of the 3,6-cis isomers was due to the occurrence of oxa-pi-allyllithium complexes 29 and 31.
(キーワード): Alkenes / Copper / Diketopiperazines / Models, Molecular / Molecular Structure / Piperazines
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jo060202z
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16709051; ● Search Scopus @ Elsevier (PMID): 16709051; ● Search Scopus @ Elsevier (DOI): 10.1021/jo060202z

(DOI: 10.1021/jo060202z, PubMed: 16709051) Ayumu Niida, Hiroaki Tanigaki, Eriko Inokuchi, Yoshikazu Sasaki, Shinya Oishi, Hiroaki Ohno, Hirokazu Tamamura, Zixuan Wang, C Stephene Peiper, Kazuo Kitaura, Akira Otaka and Nobutaka Fujii :
Stereoselective Synthesis of 3,6-Disubstituted-3,6-dihydropyridin-2-ones as Potential Diketopiperazine Mimetics Using Organocopper-Mediated anti-SN2' Reactions and Their Use in the Preparation of Low-Molecule CXCR4 Antagonists.,
The Journal of Organic Chemistry, Vol.71, No.10, 3942-3951, 2006.

(要約): Organocopper-mediated anti-SN2' reactions of gamma-phosphoryloxy-alpha,beta-unsaturated-delta-lactams were used to prepare highly functionalized diketopiperazine mimetics. The substrate phosphates 24, 32, and 47 were prepared from alpha-amino acid-derived allylic alcohols 10 by a sequence of reactions that included ring-closing metathesis. In the reactions of phosphates with organocopper reagents, the addition of LiCl dramatically improved anti-SN2' selectivity, indicating that an organocopper cluster containing lithium chloride plays an important role in the determination of regioselectivity. This reaction system was applied to the preparation of novel low molecular weight CXCR4-chemokine receptor antagonists.
(キーワード): Copper / Diketopiperazines / Molecular Structure / Piperazines / Pyridines / Receptors, CXCR4
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jo060390t
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16674071; ● Summary page in Scopus @ Elsevier: 2-s2.0-33646511988

(DOI: 10.1021/jo060390t, PubMed: 16674071, Elsevier: Scopus) T. Koide, Y. Nishikawa, S. Asada, C. M. Yamazaki, Y. Takahara, D. L. Homma, Akira Otaka, K. Ohtani, N. Wakamiya, K. Nagata and K. Kitagawa :
Specific recognition of the collagen triple helix by chaperone HSP47. II. The HSP47-binding structural motif in collagens and related proteins,
The Journal of Biological Chemistry, Vol.281, No.16, 11177-11185, 2006.

(要約): The endoplasmic reticulum-resident chaperone heat-shock protein 47 (HSP47) plays an essential role in procollagen biosynthesis. The function of HSP47 relies on its specific interaction with correctly folded triple-helical regions comprised of Gly-Xaa-Yaa repeats, and Arg residues at Yaa positions have been shown to be important for this interaction. The amino acid at the Yaa position (Yaa(-3)) in the N-terminal-adjoining triplet containing the critical Arg (defined as Arg(0)) was also suggested to be directly recognized by HSP47 (Koide, T., Asada, S., Takahara, Y., Nishikawa, Y., Nagata, K., and Kitagawa, K. (2006) J. Biol. Chem. 281, 3432-3438). Based on this finding, we examined the relationship between the structure of Yaa(-3) and HSP47 binding using synthetic collagenous peptides. The results obtained indicated that the structure of Yaa(-3) determined the binding affinity for HSP47. Maximal binding was observed when Yaa(-3) was Thr. Moreover, the required relative spatial arrangement of these key residues in the triple helix was analyzed by taking advantage of heterotrimeric collagen-model peptides, each of which contains one Thr(-3) and one Arg(0). The results revealed that HSP47 recognizes the Yaa(-3) and Arg(0) residues only when they are on the same peptide strand. Taken together, the data obtained led us to define the HSP47-binding structural epitope in the collagen triple helix and also define the HSP47-binding motif in the primary structure. A motif search against human protein database predicted candidate clients for this molecular chaperone. The search result indicated that not all collagen family proteins require the chaperoning by HSP47.
(キーワード): Amino Acid Motifs / Amino Acid Sequence / Animals / Arginine / Binding, Competitive / Cell Line / Circular Dichroism / Collagen / Computational Biology / Databases, Protein / Endoplasmic Reticulum / Epitopes / Escherichia coli / Glutathione Transferase / HSP47 Heat-Shock Proteins / Humans / Inhibitory Concentration 50 / Mice / Models, Molecular / Molecular Chaperones / Molecular Sequence Data / Peptides / Protein Binding / Protein Conformation / Protein Structure, Tertiary / Recombinant Proteins / Software / Temperature / Time Factors
(出版サイトへのリンク): ● Publication site (DOI): 10.1074/jbc.M601369200
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16484215; ● Search Scopus @ Elsevier (PMID): 16484215; ● Search Scopus @ Elsevier (DOI): 10.1074/jbc.M601369200

(DOI: 10.1074/jbc.M601369200, PubMed: 16484215) M Nakano, T Hamada, T Hayashi, S Yonemitsu, L Miyamoto, T Toyoda, S Tanaka, H Masuzaki, K Ebihara, Y Ogawa, K Hosoda, G Inoue, Y Yoshimasa, Akira Otaka, T Fushiki and K Nakao :
a2 Isoform-specific activation of 5 adenosine monophosphate-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-b-D-ribonucleoside at a physiological level activates glucose transport and increases glucose transporter 4 in mouse skeletal muscle,
Metabolism: Clinical and Experimental, Vol.55, No.3, 300-308, 2006.

(要約): 5'Adenosine monophosphate-activated protein kinase (AMPK) has been implicated in exercise-induced stimulation of glucose metabolism in skeletal muscle. Although skeletal muscle expresses both the alpha1 and alpha2 isoforms of AMPK, the alpha2 isoform is activated predominantly in response to moderate-intensity endurance exercise in human and animal muscles. The purpose of this study was to determine whether activation of alpha2 AMPK plays a role in increasing the rate of glucose transport, promoting glucose transporter 4 (GLUT4) expression, and enhancing insulin sensitivity in skeletal muscle. To selectively activate the alpha2 isoform, we used 5-aminoimidazole-4-carboxamide-1-beta-d-ribonucleoside (AICAR), which is metabolized in muscle cells and preferentially stimulates the alpha2 isoform. Subcutaneous administration of 250 mg/kg AICAR activated the alpha2 isoform for 90 minutes, but not the alpha1 isoform in hind limb muscles of the C57/B6J mouse. The maximal activation of the alpha2 isoform was observed 30 to 60 minutes after administration of AICAR and was similar to the activation induced by a 30-minute swim in a current pool. The increase in alpha2 activity paralleled the phosphorylation of Thr(172), the essential residue for full kinase activation, and the activity of acetyl-coenzyme A carboxylase beta, a known substrate of AMPK in skeletal muscle. Subcutaneous injection of AICAR rapidly increased, by 30%, the rate of 2-deoxyglucose (2DG) transport into soleus muscle; 2DG transport increased within 30 minutes and remained elevated for 4 hours after administration of AICAR. Repeated intraperitoneal injection of AICAR, 3 times a day for 4 to 7 days, increased soleus GLUT4 protein by 30% concomitant with a significant 20% increase in insulin-stimulated 2DG transport. These data suggest that moderate endurance exercise promotes glucose transport, GLUT4 expression, and insulin sensitivity in skeletal muscle at least partially via activation of the alpha2 isoform of AMPK.
(キーワード): AMP-Activated Protein Kinases / Aminoimidazole Carboxamide / Animals / Biological Transport / Deoxyglucose / Enzyme Activation / Glucose / Glucose Transporter Type 4 / Insulin / Isoenzymes / Mice / Mice, Inbred C57BL / Multienzyme Complexes / Muscle, Skeletal / Physical Conditioning, Animal / Protein-Serine-Threonine Kinases / Ribonucleosides / Up-Regulation
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.metabol.2005.09.003
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16483872; ● Search Scopus @ Elsevier (PMID): 16483872; ● Search Scopus @ Elsevier (DOI): 10.1016/j.metabol.2005.09.003

(DOI: 10.1016/j.metabol.2005.09.003, PubMed: 16483872) Ayumu Niida, Kenji Tomita, Makiko Mizumoto, Hiroaki Tanigaki, Tomohiro Terada, Shinya Oishi, Akira Otaka, Ken-ichi Inui and Nobutaka Fujii :
Unequivocal Synthesis of (Z)-Alkene and (E)-Fluoroalkene Dipeptide Isosters to Probe Structural Requirements of Peptide Transporter PEPT1.,
Organic Letters, Vol.8, No.4, 613-616, 2006.

(要約): [reaction: see text] Described is a novel synthetic route for dipeptide isosteres containing (Z)-alkene and (E)-fluoroalkene units as cis-amide bond equivalents via organocopper-mediated reduction of gamma-acetoxy- or gamma,gamma-difluoro-alpha,beta-unsaturated-delta-lactams. The synthesized isosteres were evaluated in terms of their affinities for the peptide transporter PEPT1. trans-Amide isosteres tended to possess higher affinities for PEPT1 as compared to the corresponding cis-amide bond equivalents.
(キーワード): Alkenes / Dipeptides / Hydrocarbons, Fluorinated / Molecular Structure / Stereoisomerism / Symporters
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/ol052781k
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16468724; ● Search Scopus @ Elsevier (PMID): 16468724; ● Search Scopus @ Elsevier (DOI): 10.1021/ol052781k

(DOI: 10.1021/ol052781k, PubMed: 16468724) Shinya Ohishi, Kazuhide Miyamoto, Ayumu Niida, Mikiko Yamamoto, Keiichi Ajito, Hirokazu Tamamura, Akira Otaka, Yoshihiro Kuroda, Akira Asai and Fujii Nobutaka :
Application of Tri- and Tetrasubstituted Alkene Dipeptide Mimetics to Conformational Studies of Cyclic RGD Peptides.,
Tetrahedron, Vol.62, No.7, 1416-1424, 2006.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tet.2005.11.033
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-30744436815

(DOI: 10.1016/j.tet.2005.11.033, Elsevier: Scopus) Yusuke Ohta, Saori Itoh, Akira Shigenaga, Saori Shintaku, Nobutaka Fujii and Akira Otaka :
Cysteine-Derived S-Protected Oxazolidinones: Potential Chemical Devices for the Preparation of Peptide Thioesters,
Organic Letters, Vol.8, No.3, 467-470, 2006.

(要約): [reaction: see text]. An N-S acyl-transfer-mediated preparation of peptide thioesters using the S-protected oxazolidinone derived from cysteine has been developed and applied to the synthesis of a 32-mer biologically active peptide by native chemical ligation protocols.
(キーワード): Cysteine / Esters / 分子構造 (molecular structure) / Oxazolidinones / Peptides / Sulfur Compounds
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/ol052755m
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16435861; ● Summary page in Scopus @ Elsevier: 2-s2.0-32644438516

(DOI: 10.1021/ol052755m, PubMed: 16435861, Elsevier: Scopus) Ayumu Niida, Zixuan Wang, Kenji Tomita, Shinya Oishi, Hirokazu Tamamura, Akira Otaka, Jean-Marc Navenot, James R. Broach, Stephen C. Peiper and Nobutaka Fujii :
Design and synthesis of downsized metastin (45-54) analogs with maintenance of high GPR54 agonistic activity,
Bioorganic & Medicinal Chemistry Letters, Vol.16, No.1, 134-137, 2006.

(要約): Metastin has been identified as a metastasis suppressor gene product that mediates its function through a G protein coupled receptor, GPR54. To refine insight into the critical pharmacophore for the activation of GPR54, we have conducted alanine and d-amino acid scanning on a biologically active metastin fragment (45-54). Based on these data and structures of peptides previously reported to activate GPR54, a series of shortened metastin (45-54) derivatives were synthesized and tested for the ability to induce GPR54 signaling. These biological experiments were performed in yeast containing human GPR54 that was coupled to the pheromone response pathway and a pheromone responsive lacZ reporter gene. Compounds 32, 33, and 39, which possess an N-terminal basic group and a C-terminal RW-amide motif, were strong agonists, similar to the level of metastin. This may provide an approach to reverse the pro-metastatic effect of metastin deletion in multiple malignant tumors.
(キーワード): Amino Acid Motifs / Amino Acid Sequence / Chemistry, Pharmaceutical / Dose-Response Relationship, Drug / Drug Design / Fungal Proteins / Genes, Reporter / Humans / Kisspeptins / Lac Operon / Models, Chemical / Molecular Sequence Data / Neoplasms / Peptides / Pheromones / Protein Binding / Protein Structure, Tertiary / Proteins / Receptors, G-Protein-Coupled / Receptors, Galanin / Tumor Suppressor Proteins
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bmcl.2005.09.054
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16242330; ● Summary page in Scopus @ Elsevier: 2-s2.0-27744543258

(DOI: 10.1016/j.bmcl.2005.09.054, PubMed: 16242330, Elsevier: Scopus) Hirokazu Tamamura, Ai Esaka, Teppei Ogawa, Takanobu Araki, Satoshi Ueda, Zixuan Wang, John O. Trent, Hiroshi Tsutsumi, Hiroyuki Masuno, Hideki Nakashima, Naoki Yamamoto, Stephen C. Peiper, Akira Otaka and Nobutaka Fuji :
Structure activity relationship studies on CXCR4 antagonists having cyclic pentapeptide scaffolds,
Organic & Biomolecular Chemistry, Vol.3, No.24, 4392-4394, 2005.

(要約): Structure-activity relationship studies on CXCR4 antagonists, which were previously found by using cyclic pentapeptide libraries, were performed to optimize side-chain functional groups, involving conformationally constrained analogues. In addition, a new lead of cyclic pentapeptides with the introduction of a novel pharmacophore was developed.
(キーワード): Inhibitory Concentration 50 / Molecular Structure / Peptides, Cyclic / Receptors, CXCR4 / Structure-Activity Relationship
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/b513145f
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16327900; ● Search Scopus @ Elsevier (PMID): 16327900; ● Search Scopus @ Elsevier (DOI): 10.1039/b513145f

(DOI: 10.1039/b513145f, PubMed: 16327900) Satoshi Ueda, Mizuno Fujita, Hirokazu Tamamura, Nobutaka Fujii and Akira Otaka :
Photolabile Protection for One-Pot Sequential Native Chemical Ligation,
ChemBioChem, Vol.6, No.11, 1983-1986, 2005.

(キーワード): Molecular Structure / Peptides / Photolysis
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/cbic.200500272
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16206319; ● Search Scopus @ Elsevier (PMID): 16206319; ● Search Scopus @ Elsevier (DOI): 10.1002/cbic.200500272

(DOI: 10.1002/cbic.200500272, PubMed: 16206319) Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Development of Anti-HIV Agents Targeting Dynamic Supramolecular Mechanism: Entry and Fusion Inhibitors Based on CXCR4/CCR5 Antagonists and gp41-C34-Remodeling Peptides,
Current HIV Research, Vol.3, No.4, 289-301, 2005.

(要約): A molecular mechanism involved both in HIV-entry and -fusion steps has been disclosed in detail: The interaction of an HIV envelope protein, gp120, with chemokine receptors, CXCR4 and CCR5, which were identified as major co-receptors in association with CD4, triggers conformational changes in the gp120-gp41 (another envelope protein) complex, and subsequently forms the trimer-of-hairpins structure of gp41 followed by virus-cell membrane fusion. The elucidation of the above dynamic supramolecular mechanism in HIV-entry and -fusion has provided insights into new type of drugs that can block HIV infection. Based on this, we have developed not only coreceptor antagonists (1) but also fusion inhibitors (2). (1) Potent CXCR4 antagonists, T22 and T140, have been developed through the structure-activity relationship studies on tachyplesins and polyphemusins that are horseshoe crabs' antimicrobial peptides. T22, which was initially found to bind gp120 and CD4, and T140 selectively suppress T-cell line-tropic HIV-1 (X4-HIV-1) entry based on their specific binding to CXCR4. Furthermore, molecular-size reduction of T140 using cyclic pentapeptide templates brought us to find low molecular weight CXCR4 antagonists, such as FC131. (2) Artificial remodeling of a gp41 fragment, C34, has led to development of strong inhibitors of HIV-fusion into cells. These fusion inhibitors effectively block the formation of the trimer-of-hairpins structure of gp41. HIV-entry/fusion inhibitors such as CXCR4 antagonists and C34 analogs would improve the clinical chemotherapy of AIDS and HIV-infected patients. This review article focuses on our recent research on the development of the above two types of inhibitors, including comparative studies with several CXCR4 antagonists besides T22/T140-related compounds and other fusion inhibitors such as Fuzeon (T-20).
(キーワード): Amino Acid Sequence / HIV Envelope Protein gp41 / HIV Fusion Inhibitors / Humans / Molecular Sequence Data / Oligopeptides / Peptide Fragments / Receptors, CCR5 / Receptors, CXCR4
(出版サイトへのリンク): ● Publication site (DOI): 10.2174/157016205774370429
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16250877; ● Search Scopus @ Elsevier (PMID): 16250877; ● Search Scopus @ Elsevier (DOI): 10.2174/157016205774370429

(DOI: 10.2174/157016205774370429, PubMed: 16250877) Ayumu Niida, Shinya Oishi, Yoshikazu Sasaki, Makiko Mizumoto, Hirokazu Tamamura, Nobutaka Fujii and Akira Otaka :
Facile access to (Z)-alkene-containing diketopiperazine mimetics utilizing organocopper-mediated anti-S_N2 reactions,
Tetrahedron Letters, Vol.46, No.24, 4183-4186, 2005.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.tetlet.2005.04.057
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/j.tetlet.2005.04.057

(DOI: 10.1016/j.tetlet.2005.04.057) Hirokazu Tamamura, Takanobu Araki, Satoshi Ueda, Zixuan Wang, Shinya Oishi, Ai Esaka, John O. Trent, Hideki Nakashima, Naoki Yamamoto, Stephen C. Peiper, Akira Otaka and Nobutaka Fujii :
Identification of Novel Low Molecular Weight CXCR4 Antagonists by Structural Tuning of Cyclic Tetrapeptide Scaffolds,
Journal of Medicinal Chemistry, Vol.48, No.9, 3280-3289, 2005.

(要約): A highly potent CXCR4 antagonist, compound 2, was previously found by using two orthogonal cyclic pentapeptide libraries involving conformation-based and sequence-based libraries based on the pharmacophore of a 14-mer peptidic antagonist, 1. Herein, cyclic tetrapeptides derived from replacements of the dipeptide unit (Nal-Gly) with a gamma-amino acid and pseudopeptides cyclized by disulfide and olefin bridges were synthesized to find novel scaffold structures different from that of cyclic pentapeptides. These compounds contain a reduced number of peptide bonds compared to compound 2. Furthermore, several analogues with chemical modification of the side chain of Arg(4) in 2 were also prepared. From these, several new leads possessing high to moderate CXCR4-antagonistic activity were characterized.
(キーワード): Alkenes / Animals / Arginine / Binding, Competitive / CHO Cells / Cricetinae / Cricetulus / Models, Molecular / Molecular Mimicry / Oligopeptides / Peptides, Cyclic / Radioligand Assay / Receptors, CXCR4 / Stereoisomerism / Structure-Activity Relationship / Sulfides
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jm050009h
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15857134; ● Search Scopus @ Elsevier (PMID): 15857134; ● Search Scopus @ Elsevier (DOI): 10.1021/jm050009h

(DOI: 10.1021/jm050009h, PubMed: 15857134) Hirokazu Tamamura, Kenichi Hiramatsu, Satoshi Ueda, Zixuan Wang, Shuichi Kusano, Shigemi Terakubo, John O. Trent, Stephen C. Peiper, Naoki Yamamoto, Hideki Nakashima, Akira Otaka and Nobutaka Fujii :
Stereoselective Synthesis of [L-Arg-L/D-3-(2-naphthyl)alanine]-Type (E)-Alkene Dipeptide Isosteres and Its Application to the Synthesis and Biological Evaluation of Pseudopeptide Analogues of the CXCR4 Antagonist FC131,
Journal of Medicinal Chemistry, Vol.48, No.2, 380-391, 2005.

(要約): L,L-Type and L,D-type (E)-alkene dipeptide isosteres (EADIs) that have unnatural side chains at the alpha-position were synthesized by the combination of stereoselective aziridinyl ring-opening reactions and organozinc-copper-mediated anti-S(N)2' reactions toward a single substrate of gamma,delta-cis-gamma,delta-epimino (E)-alpha,beta-enoate. The utility of this methodology was demonstrated by the stereoselective synthesis of a set of diastereomeric EADIs of L-Arg-L/D-3-(2-naphthyl)alanine (Nal) that is contained in a small CXCR4 antagonist FC131 [cyclo(-D-Tyr-Arg-Arg-Nal-Gly-)]. Furthermore, a (Nal-Gly)-type EADI was synthesized by samarium diiodide (SmI(2))-induced reduction of a gamma-acetoxy-alpha,beta-enoate. Several FC131 analogues, in which these EADIs were inserted for reduction of their peptide character, were synthesized with analogues containing reduced amide-type dipeptide isosteres to investigate the importance of these amide bonds for anti-HIV and CXCR4-antagonistic activity.
(キーワード): Alanine / Animals / Anti-HIV Agents / Cell Line / Cricetinae / Dipeptides / HIV-1 / Humans / Models, Molecular / Molecular Conformation / Naphthalenes / Peptides, Cyclic / Receptors, CXCR4 / Stereoisomerism / Structure-Activity Relationship
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jm049429h
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15658852; ● Search Scopus @ Elsevier (PMID): 15658852; ● Search Scopus @ Elsevier (DOI): 10.1021/jm049429h

(DOI: 10.1021/jm049429h, PubMed: 15658852) Daisuke Nameki, Eiichi Kodama, Mieko Ikeuchi, Naoto Mabuchi, Akira Otaka, Hirokazu Tamamura, Mutsuhito Ohno, Nobutaka Fujii and Masao Matsuoka :
Mutations Conferring Resistance to Human Immunodeficiency Virus Type 1 Fusion Inhibitors Are Restricted by gp41 and Rev-Responsive Element Functions,
Journal of Virology, Vol.79, No.2, 764-770, 2005.

(要約): One of the human immunodeficiency virus (HIV) envelope proteins, gp41, plays a key role in HIV fusion. A gp41-derived peptide, T-20, efficiently inhibits HIV fusion and is currently approved for treatment of HIV-infected individuals. Although resistant variants have been reported, the mechanism of the resistance remains to be defined. To elucidate the mechanism in detail, we generated variants resistant to C34, a peptide derived from the gp41 carboxyl terminus heptad repeat (C-HR) in vitro. The resistant variants had a 5-amino-acid deletion in gp120 and a total of seven amino acid substitutions in gp41. Binding assays revealed that an I37K substitution in the N-terminal heptad repeat (N-HR) impaired the binding of C34, whereas an N126K substitution in the C-HR enhanced the binding to mutated N-HR, indicating that both mutations were directly involved in resistance. On the other hand, substitutions for A30 and D36 seemed to be secondary mutations, located complementary to each other in the Rev-responsive element (RRE), and were mutated simultaneously to maintain the secondary structure of the RRE that was impaired by the mutations at I37. Thus, HIV acquired resistance to C34 by mutations in N-HR, which directly interacted with C34. However, since this region also encoded the RRE, additional mutations were required to maintain viral replication. These results suggest that HIV fusion is one of the attractive targets for HIV chemotherapy.
(キーワード): Amino Acid Sequence / Animals / COS Cells / Drug Resistance, Viral / Genes, env / HIV Envelope Protein gp41 / HIV Fusion Inhibitors / HIV-1 / Humans / Molecular Sequence Data / Mutation / Peptide Fragments / Structure-Activity Relationship / Virus Replication
(出版サイトへのリンク): ● Publication site (DOI): 10.1128/JVI.79.2.764-770.2005
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15613304; ● Search Scopus @ Elsevier (PMID): 15613304; ● Search Scopus @ Elsevier (DOI): 10.1128/JVI.79.2.764-770.2005

(DOI: 10.1128/JVI.79.2.764-770.2005, PubMed: 15613304) Hirokazu Tamamura, Miho Fujisawa, Kenichi Hiramatsu, Makiko Mizumoto, Hideki Nakashima, Naoki Yamamoto, Akira Otaka and Nobutaka Fujii :
Identification of a CXCR4 antagonist, a T140 analog, as an anti-rheumatoid arthritis agent,
FEBS Letters, Vol.569, No.1-3, 99-104, 2004.

(要約): Several recent papers support the involvement of an interaction between stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, chemokine receptor CXCR4, in memory T cell migration in the inflamed rheumatoid arthritis (RA) synovium. Analogs of the 14-mer peptide T140 were previously found to be specific CXCR4 antagonists that were characterized as not only HIV-entry inhibitors but also anti-cancer-metastatic agents. In this study, a T140 analog, 4F-benzoyl-TN14003, was proven to inhibit CXCL12-mediated migration of human Jurkat cells and mouse splenocyte in a dose-dependent manner in vitro (IC(50)=0.65 and 0.54 nM, respectively). Furthermore, slow release administration by subcutaneous injection (s.c.) of 4F-benzoyl-TN14003 using an Alzet osmotic pump significantly suppressed the delayed-type hypersensitivity response induced by sheep red blood cells in mice, and significantly ameliorated clinical severity in collagen-induced arthritis in mice. As such, T140 analogs might be attractive lead compounds for chemotherapy of RA.
(キーワード): Animals / Antirheumatic Agents / Arthritis, Rheumatoid / Cell Movement / Collagen / Humans / Jurkat Cells / Mice / Oligopeptides / Receptors, CXCR4
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.febslet.2004.05.056
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15225616; ● Search Scopus @ Elsevier (PMID): 15225616; ● Search Scopus @ Elsevier (DOI): 10.1016/j.febslet.2004.05.056

(DOI: 10.1016/j.febslet.2004.05.056, PubMed: 15225616) Taro Toyoda, Tatsuya Hayashi, Licht Miyamoto, Shin Yonemitsu, Masako Nakano, Satsuki Tanaka, Ken Ebihara, Hiroaki Masuzaki, Kiminori Hosoda, Gen Inoue, Akira Otaka, Kenji Sato, Tohru Fushiki and Kazuwa Nakao :
Possible involvement of the α1 isoform of 5'AMP-activated protein kinase in oxidative stress-stimulated glucose transport in skeletal muscle,
American Journal of Physiology, Endocrinology and Metabolism, Vol.287, No.1, E166-173, 2004.

(要約): Recent studies have suggested that 5'AMP-activated protein kinase (AMPK) is activated in response to metabolic stresses, such as contraction, hypoxia, and the inhibition of oxidative phosphorylation, which leads to insulin-independent glucose transport in skeletal muscle. In the present study, we hypothesized that acute oxidative stress increases the rate of glucose transport via an AMPK-mediated mechanism. When rat epitrochlearis muscles were isolated and incubated in vitro in Krebs buffer containing the oxidative agent H(2)O(2), AMPKalpha1 activity increased in a time- and dose-dependent manner, whereas AMPKalpha2 activity remained unchanged. The activation of AMPKalpha1 was associated with phosphorylation of AMPK Thr(172), suggesting that an upstream kinase is involved in the activation process. H(2)O(2)-induced AMPKalpha1 activation was blocked in the presence of the antioxidant N-acetyl-l-cysteine (NAC), and H(2)O(2) significantly increased the ratio of oxidized glutathione to glutathione (GSSG/GSH) concentrations, a sensitive marker of oxidative stress. H(2)O(2) did not cause an increase in the conventional parameters of AMPK activation, such as AMP and AMP/ATP. H(2)O(2) increased 3-O-methyl-d-glucose transport, and this increase was partially, but significantly, blocked in the presence of NAC. Results were similar when the muscles were incubated in a superoxide-generating system using hypoxanthine and xanthine oxidase. Taken together, our data suggest that acute oxidative stress activates AMPKalpha1 in skeletal muscle via an AMP-independent mechanism and leads to an increase in the rate of glucose transport, at least in part, via an AMPKalpha1-mediated mechanism.
(キーワード): AMP-Activated Protein Kinases / Acetylcysteine / Animals / Dose-Response Relationship, Drug / Glucose / Hydrogen Peroxide / Isoenzymes / Leucine / Male / Multienzyme Complexes / Muscle, Skeletal / Oxidative Stress / Protein-Serine-Threonine Kinases / Rats / Rats, Sprague-Dawley
(出版サイトへのリンク): ● Publication site (DOI): 10.1152/ajpendo.00487.2003
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15026306; ● Search Scopus @ Elsevier (PMID): 15026306; ● Search Scopus @ Elsevier (DOI): 10.1152/ajpendo.00487.2003

(DOI: 10.1152/ajpendo.00487.2003, PubMed: 15026306) Akira Otaka, Satoshi Ueda, Kenji Tomita, Yoshiaki Yano, Hirokazu Tamamura, Katsumi Matsuzaki and Nobutaka Fujii :
Facile synthesis of membrane-embedded peptides utilizing lipid bilayer-assisted chemical ligation,
Chemical Communications, No.15, 1722-1723, 2004.

(要約): Lipid bilayer-assisted chemical ligation between thiolester and N-terminal cysteine peptides has been developed with successful application to the synthesis of membrane protein segments possessing both two transmembrane and one extracellular regions.
(キーワード): Amino Acid Sequence / Cysteine / Esters / Ligands / Lipid Bilayers / Membrane Proteins / Molecular Sequence Data / Peptides / Sulfhydryl Compounds
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/B404008B
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15278155; ● Search Scopus @ Elsevier (PMID): 15278155; ● Search Scopus @ Elsevier (DOI): 10.1039/B404008B

(DOI: 10.1039/B404008B, PubMed: 15278155) Norio Yamamoto, Rongge Yang, Yoshiyuki Yoshinaka, Shinji Amari, Tatsuya Nakano, Jindrich Cinatl, Holger Rabenau, Hans Wilhelm Doerr, Gerhard Hunsmann, Akira Otaka, Hirokazu Tamamura, Nobutaka Fujii and Naoki Yamamoto :
HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus,
Biochemical and Biophysical Research Communications, Vol.318, No.3, 719-725, 2004.

(要約): A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.
(キーワード): Animals / Antiviral Agents / Cercopithecus aethiops / Fluorescent Antibody Technique / HIV Protease Inhibitors / Lethal Dose 50 / Nelfinavir / RNA, Viral / Ritonavir / SARS Virus / Time Factors / Vero Cells / Virus Replication
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/j.bbrc.2004.04.083
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15144898; ● Search Scopus @ Elsevier (PMID): 15144898; ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2004.04.083

(DOI: 10.1016/j.bbrc.2004.04.083, PubMed: 15144898) Hirokazu Tamamura, Makiko Mizumoto, Kenichi Hiramatsu, Shuichi Kusano, Shigemi Terakubo, Naoki Yamamoto, John O. Trent, Zixuan Wang, Stephen C. Peiper, Hideki Nakashima, Akira Otaka and Nobutaka Fujii :
Topochemical exploration of potent compounds using retro-enantiomer libraries of cyclic pentapeptides,
Organic & Biomolecular Chemistry, Vol.2, No.8, 1255-1257, 2004.

(要約): Cyclic pentapeptides have been adopted as conformationally restricted peptide templates to dispose pharmacophores of bioactive peptides. In our recent study, use of two orthogonal cyclic pentapeptide libraries involving conformation-based and sequence-based libraries containing critical residues of a bioactive peptide led to the discovery of potent downsized peptides that possess activity comparable to that of the parent peptide. The present study demonstrates that a third library consisting of retro-enantiomers (retro-inverso peptides) that possess not only all residues with the opposite configuration to those in the corresponding original peptide but also amino acid sequences with reversed arrangement, is important as an alternative library for rationally finding active compounds.
(キーワード): Amino Acid Sequence / Oligopeptides / Peptide Library / Peptides, Cyclic / Protein Conformation / Stereoisomerism / Structure-Activity Relationship
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/b401485p
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15064805; ● Search Scopus @ Elsevier (PMID): 15064805; ● Search Scopus @ Elsevier (DOI): 10.1039/b401485p

(DOI: 10.1039/b401485p, PubMed: 15064805) Akira Otaka, Junko Watanabe, Akira Yukimasa, Yoshikazu Sasaki, Hideaki Watanabe, Takayoshi Kinoshita, Shinya Oishi, Hirokazu Tamamura and Nobutaka Fujii :
SmI₂-Mediated Reduction of γ,γ-Difluoro-α,β-enoates with Application to the Synthesis of Functionalized (Z)-Fluoroalkene-Type Dipeptide Isosteres,
The Journal of Organic Chemistry, Vol.69, No.5, 1634-1645, 2004.

(要約): A samarium diiodide (SmI(2))-mediated reduction of gamma,gamma-difluoro-alpha,beta-enoates (15, 29, and 34) was successfully applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres (23, 30, and 35), which have served as potential dipeptide mimetics. Reduction of the gamma,gamma-difluoro-alpha,beta-enoates by SmI(2) proceeded via successive two-electron transfers to form dienolate species which upon kinetically controlled trapping with t-BuOH yielded Xaa-Gly-type fluoroalkene isosteres exemplified by 23, 30, and 35. Replacement of the t-BuOH kinetic trapping agent with aldehydes or ketones provided access to alpha-substituted fluoroalkene isosteres (43 and 45) through aldol reactions of Sm-dienolates with the carbonyl compounds. Of particular note, the use of the SmI(2)-HCHO reagent system with chiral enoate 34 provided D-Phe-psi[(Z)-CF[double bond]CH]-D/L-Ser isosteres (45), which could be converted to enantiomerically pure isosteres (49-52) that bore a variety of side chain functionalities at the alpha-position. This was achieved by a sequence of manipulations consisting of beta-lactone formation followed by chromatographic separation and ring-opening with soft nucleophiles. Included in the present work is the first utilization of a Rh-catalyzed Reformatsky reaction of chiral imines for the stereoselective preparation of alpha,alpha-difluoro-beta-amino acid derivatives (28 and 33). The appropriate choice of reagents (carbonyl compounds for kinetic trapping or ring-opening nucleophiles and imines for Reformatsky reactions) allows the presented methodology to yield various fluoroalkene isosteres possessing a wide range of side chain functionalities.
(キーワード): Alkenes / Dipeptides / Hydrocarbons, Fluorinated / Imines / Iodides / Magnetic Resonance Spectroscopy / Molecular Structure / Samarium / Stereoisomerism
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jo035709d
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14987023; ● Search Scopus @ Elsevier (PMID): 14987023; ● Search Scopus @ Elsevier (DOI): 10.1021/jo035709d

(DOI: 10.1021/jo035709d, PubMed: 14987023) Hirokazu Tamamura, Kenichi Hiramatsu, Makiko Mizumoto, Satoshi Ueda, Shuichi Kusano, Shigemi Terakubo, Miki Akamatsu, Naoki Yamamoto, John O. Trent, Zixuan Wang, Stephen C. Peiper, Hideki Nakashima, Akira Otaka and Nobutaka Fujii :
Enhancement of the T140-based pharmacophores leads to the development of more potent and bio-stable CXCR4 antagonists,
Organic & Biomolecular Chemistry, Vol.1, No.21, 3663-3669, 2003.

(要約): A CXCR4 antagonistic peptide, T140, and its bio-stable analogs, such as Ac-TE14011, were previously developed. These peptides inhibit the entry of T cell line-tropic strains of HIV-1 (X4-HIV-1) into T cells. Herein, a series of TE14011 analogs having modifications in the N-terminal region were synthesized to develop effective compounds with increased biostability. Among these analogs, 4F-benzoyl-TE14011 (TF14013) showed the strongest anti-HIV activity derived from CXCR4-antagonism, suggesting that a 4-fluorobenzoyl moiety at the N-terminus of T140 analogs constitutes a novel T140-based pharmacophore for CXCR4 antagonists. Structure-activity relationship (SAR) studies on TE14011 analogs with N(alpha)-acylation by several benzoic acid derivatives have disclosed a significant relationship between the anti-HIV activity and the Hammett constant (sigma) of substituted benzoic acids. TF14013 was found to be stable in mouse serum, but not completely stable in rat liver homogenate due to deletion of the C-terminal Arg14-NH2 from the parent peptide. This biodegradation was completely suppressed by N-alkyl-amidation at the C-terminus. Taken together, the enhancement of the T140-based pharmacophores led to development of a novel CXCR4 antagonist, 4F-benzoyl-TE14011-Me (TF14013-Me), which has very high anti-HIV activity and increased biostability.
(キーワード): Circular Dichroism / Oligopeptides / Protein Conformation / Receptors, CXCR4 / Spectrometry, Mass, Electrospray Ionization
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/b306613b
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14649897; ● Search Scopus @ Elsevier (PMID): 14649897; ● Search Scopus @ Elsevier (DOI): 10.1039/b306613b

(DOI: 10.1039/b306613b, PubMed: 14649897) Hirokazu Tamamura, Kenichi Hiramatsu, Shuichi Kusano, Shigemi Terakubo, Naoki Yamamoto, John O. Trent, Zixuan Wang, Stephen C. Peiper, Hideki Nakashima, Akira Otaka and Nobutaka Fujii :
Synthesis of potent CXCR4 inhibitors possessing low cytotoxicity and improved biostability based on T140 derivatives,
Organic & Biomolecular Chemistry, Vol.1, No.21, 3656-3662, 2003.

(要約): A peptidic CXCR4 antagonist T140 efficiently blocks the entry of T cell line-tropic strains of HIV-1 (X4-HIV-1) into target cells. In this study, a series of T140 derivatives, replacing the basic amino acid residues with Glu (D-Glu) and/or L-citrulline (Cit), were synthesized in order to reduce non-specific binding and cytotoxicity. Among them, TE14011 ([Cit6, D-Glu8]-T140 with the C-terminal amide) exhibited strong anti-HIV activity and low cytotoxicity. TE14011 was found to be stable in mouse serum, but unstable in rat liver homogenate due to the deletion of the N-terminal Arg1-Arg2-L-3-(2-naphthyl)alanine (Nal)3 residues from the parent peptide. N-Terminal acetylation of TE14011 led to the development of a novel lead compound, Ac-TE 14011, which possesses a high selectivity index as well as increased stability in serum and liver homogenate.
(キーワード): Amino Acid Sequence / Animals / Cell Line / Humans / Mice / Molecular Sequence Data / Oligopeptides / Receptors, CXCR4 / T-Lymphocytes
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/b306473p
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14649896; ● Search Scopus @ Elsevier (PMID): 14649896; ● Search Scopus @ Elsevier (DOI): 10.1039/b306473p

(DOI: 10.1039/b306473p, PubMed: 14649896) Hirokazu Tamamura, Akira Hori, Naoyuki Kanzaki, Kenichi Hiramatsu, Makiko Mizumoto, Hideki Nakashima, Naoki Yamamoto, Akira Otaka and Fujii Nobutaka :
T140 analogs as CXCR4 antagonists identified as anti-metastatic agents in the treatment of breast cancer,
FEBS Letters, Vol.550, No.3, 79-83, 2003.

(要約): A chemokine receptor, CXCR4, and its endogenous ligand, stromal cell-derived factor-1 (SDF-1), have been recognized to be involved in the metastasis of several types of cancers. T140 analogs are peptidic CXCR4 antagonists composed of 14 amino acid residues that were previously developed as anti-HIV agents having inhibitory activity against HIV-entry through its co-receptor, CXCR4. Herein, we report that these compounds effectively inhibited SDF-1-induced migration of human breast cancer cells (MDA-MB-231), human leukemia T cells (Sup-T1) and human umbilical vein endothelial cells at concentrations of 10-100 nM in vitro. Furthermore, slow release administration by subcutaneous injection using an Alzet osmotic pump of a potent and bio-stable T140 analog, 4F-benzoyl-TN14003, gave a partial, but statistically significant (P</=0.05 (t-test)) reduction in pulmonary metastasis of MDA-MB-231 in SCID mice, even though no attempt was made to inhibit other important targets such as CCR7. These results suggest that T140 analogs have potential use for cancer therapy, and that small molecular CXCR4 antagonists could potentially replace neutralizing antibodies as anti-metastatic agents for breast cancer.
(キーワード): Animals / Antineoplastic Agents / Breast Neoplasms / Cell Movement / Chemokine CXCL12 / Chemokines, CXC / Drug Screening Assays, Antitumor / Endothelium, Vascular / Female / Gene Expression Regulation, Neoplastic / Humans / Jurkat Cells / Lung Neoplasms / Mice / Mice, SCID / Neoplasm Metastasis / Oligopeptides / Peptides / RNA, Messenger / Receptors, CCR7 / Receptors, CXCR4 / Receptors, Chemokine / Tumor Cells, Cultured
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0014-5793(03)00824-X
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12935890; ● Search Scopus @ Elsevier (PMID): 12935890; ● Search Scopus @ Elsevier (DOI): 10.1016/S0014-5793(03)00824-X

(DOI: 10.1016/S0014-5793(03)00824-X, PubMed: 12935890) Akira Otaka, Akira Yukimasa, Junko Watanabe, Yoshikazu Sasaki, Sinya Oishi, Hirokazu Tamamura and Nobutaka Fujii :
Application of samarium diiodide (SmI2)-induced reduction of γ-acetoxy-α,β-enoates with α-specific kinetic electrophilic trapping for the synthesis of amino acid derivatives,
Chemical Communications, No.15, 1834-1835, 2003.

(要約): Gamma-acetoxy-alpha,beta-enoates were easily reduced by samarium diiodide (SmI2) in THF to generate samarium dienolates which were kinetically trapped with ease at their alpha-positions by electrophiles (proton, aldehydes or ketones) to yield (E)-alkene dipeptide isosteres or gamma-amino acid derivatives in high chemical yields.
(キーワード): Acetates / Amino Acids / Iodides / Kinetics / Models, Chemical / Organometallic Compounds / Oxidation-Reduction / Samarium / Stereoisomerism
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/b303718e
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12931990; ● Summary page in Scopus @ Elsevier: 2-s2.0-0041667790

(DOI: 10.1039/b303718e, PubMed: 12931990, Elsevier: Scopus) Nobutaka Fujii, Shinya Oishi, Kenichi Hiramatsu, Takanobu Araki, Satoshi Ueda, Hirokazu Tamamura, Akira Otaka, Shuichi Kusano, Shigemi Terakubo, Hideki Nakashima, James A. Broach, John O. Trent, Zi-xuan Wang and Stephen C. Peiper :
Molecular-Size Reduction of a Potent CXCR4-Chemokine Antagonist Using Orthogonal Combination of Conformation- and Sequence-Based Libraries,
Angewandte Chemie International Edition, Vol.42, No.28, 3251-3253, 2003.

(キーワード): Amino Acid Sequence / Oligopeptides / Peptide Library / Peptides, Cyclic / Protein Conformation / Receptors, CXCR4
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/anie.200351024
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12876735; ● Search Scopus @ Elsevier (PMID): 12876735; ● Search Scopus @ Elsevier (DOI): 10.1002/anie.200351024

(DOI: 10.1002/anie.200351024, PubMed: 12876735) Hirokazu Tamamura, Terukazu Kato, Akira Otaka and Nobutaka Fujii :
Synthesis of potent beta-secretase inhibitors containing a hydroxyethylamine dipeptide isostere and their structure-activity relationship studies,
Organic & Biomolecular Chemistry, Vol.1, No.14, 2468-2473, 2003.

(要約): Several beta-secretase inhibitors were designed based on hydroxyethylamine dipeptide isostere (HDI) structures and were synthesized by a methodology using the aza-Payne rearragement and O,N-acyl transfer reactions to study their structure-activity relationships. Among these pseudopeptides, effective compounds were developed as the first beta-secretase inhibitors containing the HDI transition state mimic with potent enzyme inhibitory activity (IC50 < 100 nM).
(キーワード): Acylation / Amino Acid Sequence / Aspartic Acid Endopeptidases / Aza Compounds / Dipeptides / Esterification / Ethylamines / Humans / Inhibitory Concentration 50 / Isoenzymes / Molecular Mimicry / Oligopeptides / Protease Inhibitors / Recombinant Proteins / 構造活性相関 (structureactivity relationship)
(出版サイトへのリンク): ● Publication site (DOI): 10.1039/b304842j
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12956063; ● Search Scopus @ Elsevier (PMID): 12956063; ● Search Scopus @ Elsevier (DOI): 10.1039/b304842j

(DOI: 10.1039/b304842j, PubMed: 12956063) Hirokazu Tamamura, Yasuhiro Koh, Satoshi Ueda, Yoshikazu Sasaki, Tomonori Yamasaki, Manabu Aoki, Kenji Maeda, Yoriko Watai, Hisashi Arikuni, Akira Otaka, Hiroaki Mitsuya and Nobutaka Fujii :
Reduction of Peptide Character of HIV Protease Inhibitors That Exhibit Nanomolar Potency against Multidrug Resistant HIV-1 Strains,
Journal of Medicinal Chemistry, Vol.46, No.9, 1764-1768, 2003.

(要約): Novel HIV protease inhibitors containing a hydroxyethylamine dipeptide isostere as a transition state-mimic king structure were synthesized by combining substructures of known HIV protease inhibitors. Among them, TYA5 and TYB5 were proven to be not only potent enzyme inhibitors (K(i) = 0.12 nM and 0.10 nM, respectively) but also strong anti-HIV agents (IC(50) = 9.5 nM and 66 nM, respectively), even against viral strains with multidrug resistance. Furthermore, insertion of an (E)-alkene dipeptide isostere at the P(1)-P(2) position of TYB5 led to development of a purely nonpeptidic protease inhibitor, TYB1 (K(i) = 0.38 nM, IC(50) = 160 nM).
(キーワード): Dipeptides / Drug Resistance, Multiple, Viral / HIV Protease Inhibitors / HIV-1 / Isoquinolines / Molecular Mimicry / Naphthalenes / Stereoisomerism / Structure-Activity Relationship / Sulfonamides
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jm020537i
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12699395; ● Search Scopus @ Elsevier (PMID): 12699395; ● Search Scopus @ Elsevier (DOI): 10.1021/jm020537i

(DOI: 10.1021/jm020537i, PubMed: 12699395) Shinya Oishi, Takae Kamano, Ayumu Niida, Yoshihiko Odagaki, Nobuyuki Hamanaka, Mikio Yamamoto, Keiichi Ajito, Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Diastereoselective Synthesis of New Ψ [(E)-CH=CMe]- and Ψ [(Z)-CH=CMe]-type Alkene Dipeptide Isosteres by Organocopper Reagents and Application to Conformationally Restricted Cyclic RGD Peptidomimetics,
The Journal of Organic Chemistry, Vol.67, No.17, 6162-6173, 2002.

(要約): Diastereoselective synthesis of new psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type alkene dipeptide isosteres corresponding to dipeptides having one N-methylamino acid, and application to bioactive peptides, are described. In a key reaction introducing the chiral alpha-alkyl group of the isosteres, organocopper-mediated alkylation of syn-beta-methylated gamma-mesyloxy-alpha,beta-enoate 26a afforded E- and Z-isomers of anti-S(N)2' products in a solvent-dependent manner. The resulting two isosteres, D-Phe-psi[(E)-CH=CMe]-L-Val 27a and D-Phe-psi[(Z)-CH=CMe]-L-Val 28b, which corresponded to trans- and cis-conformers of D-Phe-L-MeVal, respectively, were utilized in a structure-activity relationship study on cyclic RGD peptides 1 and 2, in company with a psi[(E)-CH=CH]-type alkene dipeptide isostere, D-Phe-psi[(E)-CH=CH]-L-Val. The cyclic isostere-containing pseudopeptides 3, 4, and 40 were synthesized and biological activity against integrin alpha(V)beta(3) and alpha(IIb)beta(3) receptors were also evaluated.
(キーワード): Alkenes / Chemistry, Organic / Copper / Cyclization / Dipeptides / Molecular Mimicry / Molecular Structure / Organometallic Compounds / Proline / Stereoisomerism
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jo025923m
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12182657; ● Search Scopus @ Elsevier (PMID): 12182657; ● Search Scopus @ Elsevier (DOI): 10.1021/jo025923m

(DOI: 10.1021/jo025923m, PubMed: 12182657) Akira Otaka, Fumihiko Katagiri, Takayoshi Kinoshita, Yoshihiko Odagaki, Shinya Oishi, Hirokazu Tamamura, Nobuyuki Hamanaka and Nobutaka Fujii :
Regio- and Stereoselective Synthesis of (E)-Alkene trans-Xaa-Pro Dipeptide Mimetics Utilizing Organocopper-Mediated Anti-SN2' Reactions,
The Journal of Organic Chemistry, Vol.67, No.17, 6152-6161, 2002.

(要約): Proline dipeptides (Xaa-Pro) exist as an equilibrium mixture of cis- and trans-rotamers, which depends on the energy barriers for imide isomerization. This conformation mixture contributes to both structure and function of proline-containing peptides and proteins. Structural motifs resembling these cis- or trans-conformers have served as useful tools for elucidating contributions of proline residues in the physicochemical and biological profiles of structures which contain them. Among such motifs are alkene dipeptide isosteres which mimic cis- or trans-imide using (Z)- or (E)-alkene, respectively. In this report, the first regio- and stereoselective syntheses of (E)-alkene dipeptide isosteres (20, 31, and 35) corresponding to trans-proline dipeptides are described. Key to the synthesis of these mimetics is the anti-S(N)2' reaction of vinyl aziridines such as 15 or vinyl oxazolidinones such as 28 and 32 with organocopper reagents "RCu" (R = CH(2)SiMe(2)(Oi-Pr)). Reaction of cis-vinylaziridine 15 derived from L-serine with organocopper reagent gave a precursor of the trans-L-Ser-D-Pro type alkene isosteres 20, accompanied by an S(N)2 side product. One limitation with the use of such aziridine-mediated methodology is formation of the corresponding trans-aziridine 22, which leads to L-L type isosteres, that is unstable and obtainable only in low yield. On the other hand, both isomers of oxazolidinone derivatives can be easily obtained from N-Boc-protected amino alcohols. The reaction of trans- 28 or cis-oxazolidinone derivative 32 with organocopper reagents proceeds quantitatively with high regio- and diastereoselectivities in anti-S(N)2' fashion. Subsequent oxidative treatment of the newly introduced isopropoxydimethylsilylmethyl group yields trans-L-Ser-L-Pro 31 or trans-L-Ser-D-Pro type isosteres 35, respectively. Of note, synthesized isostere 31 can also be converted to trans-phosphoSer-Pro 42 and trans-Cys-Pro mimetics 44. The present synthetic methodology affords trans-Xaa-Pro alkene-type dipeptide isosteres in high yield with relatively simple manipulation.
(キーワード): Alkenes / Chemistry, Organic / Copper / Dipeptides / Molecular Mimicry / Molecular Structure / Organometallic Compounds / Proline / Stereoisomerism
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jo025922u
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12182656; ● Search Scopus @ Elsevier (PMID): 12182656; ● Search Scopus @ Elsevier (DOI): 10.1021/jo025922u

(DOI: 10.1021/jo025922u, PubMed: 12182656) Akira Otaka, Miki Nakamura, Daisuke Nameki, Eiichi Kodama, Susumu Uchiyama, Syota Nakamura, Hiroaki Nakano, Hirokazu Tamamura, Yuji Kobayashi, Masao Matsuoka and Nobutaka Fujii :
Remodeling of gp41-C34 Peptide Leads to Highly Effective Inhibitors of the Fusion of HIV-1 with Target Cells,
Angewandte Chemie International Edition, Vol.41, No.16, 2937-2940, 2002.

(キーワード): Amino Acid Sequence / Anti-HIV Agents / Drug Design / HIV Envelope Protein gp41 / HIV-1 / Humans / Molecular Sequence Data / Peptide Fragments / Structure-Activity Relationship
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/1521-3773(20020816)41:16<2937::AID-ANIE2937>3.0.CO;2-J
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12203417; ● Search Scopus @ Elsevier (PMID): 12203417; ● Search Scopus @ Elsevier (DOI): 10.1002/1521-3773(20020816)41:16<2937::AID-ANIE2937>3.0.CO;2-J

(DOI: 10.1002/1521-3773(20020816)41:16<2937::AID-ANIE2937>3.0.CO;2-J, PubMed: 12203417) Masayoshi Makino, Ikuko Okazaki, Shingo Kasai, Norio Nishi, Maria Bougaeva, Benjamin S. Weeks, Akira Otaka, Peter K. Nielsen, Yoshihiko Yamada and Motoyoshi Nomizu :
Identification of Cell Binding Sites in the Laminin α5-Chain G Domain,
Experimental Cell Research, Vol.277, No.1, 95-106, 2002.

(要約): The laminins consist of at least 11 polypeptides (5 alpha-chains, 3 beta-chains, and 3 gamma-chains) specific to basement membranes. Here we investigate the biological activity associated with the G domain of the newly identified laminin alpha5-chain using 113 overlapping synthetic peptides (positions 2679-3635). Using HT-1080 cells, 21 peptides showed attachment activity either on peptide-coated tissue culture plates or to peptide-conjugated Sepharose beads. Heparin inhibited cell attachment to 16 peptides, while ethylenediaminetetraacetic acid exhibited no inhibitory activity. Peptides A5G-27, A5G-65, and A5G-71 showed the strongest cell attachment, with the minimum active core sequences of the peptides being GIIFFL, HQNMGSVNVSV, and YLQFVG, respectively. Furthermore, these 16 peptides were tested for their ability to stimulate neurite outgrowth in the PC12 cells. A5G-3, A5G-33, A5G-71, A5G-73, A5G-81, and A5G-101 were the only peptides of the 16 that demonstrated the ability to promote neurite outgrowth. These results demonstrate that synthetic peptides with alpha5-chain G domain primary amino acid sequences possess some of the same biological activities attributable to the whole laminin and the alpha5-chain G domain. Therefore, these peptides may be useful in the investigation of laminin-receptor interactions and possibly mechanisms of laminin signal transduction.
(キーワード): Amino Acid Sequence / Animals / Binding Sites / Cell Division / Humans / Laminin / Molecular Sequence Data / Neurites / PC12 Cells / Peptides / Plastics / Protein Structure, Tertiary / Rats / Recombinant Fusion Proteins / Sepharose / Tumor Cells, Cultured
(出版サイトへのリンク): ● Publication site (DOI): 10.1006/excr.2002.5540
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12061820; ● Summary page in Scopus @ Elsevier: 2-s2.0-18544365848

(DOI: 10.1006/excr.2002.5540, PubMed: 12061820, Elsevier: Scopus) Hirokazu Tamamura, Akane Omagari, Kenichi Hiramatsu, Shinya Oishi, Hiromu Habashita, Taisei Kanamoto, Kazuyo Gotoh, Naoki Yamamoto, Hideki Nakashima, Akira Otaka and Nobutaka Fujii :
Certification of the Critical Importance of L-3-(2-Naphthyl)alanine at Position 3 of a Specific CXCR4 Inhibitor, T140, Leads to an Exploratory Performance of Its Downsizing Study,
Bioorganic & Medicinal Chemistry, Vol.10, No.5, 1417-1426, 2002.

(要約): We have previously found that a 14-amino acid residue-peptide, T140, inhibits infection of target cells by T cell line-tropic HIV-1 (X4-HIV-1) through its specific binding to a chemokine receptor, CXCR4. Here, the importance of an L-3-(2-naphthyl)alanine (Nal) residue at position 3 in T140 for high anti-HIV activity and inhibitory activity against Ca(2+) mobilization induced by stromal cell-derived factor (SDF)-1alpha-stimulation through CXCR4 has initially been shown by the synthesis and biological evaluation of several analogues, where Nal(3) is substituted by diverse aromatic amino acids. Next, the order of the N-terminal 3 residues (Arg(1)-Arg(2)-Nal(3)) has been proved to be important from the structure--activity relationship (SAR) study shuffling these residues. Based on these results, we have found 10-residue peptides possessing modest anti-HIV activity by systematic antiviral evaluation of a series of synthetic, shortened analogues of T140.
(キーワード): Alanine / Amino Acid Sequence / Anti-HIV Agents / Calcium Signaling / Cell Survival / HIV-1 / Humans / Naphthalenes / Oligopeptides / Receptors, CXCR4 / Structure-Activity Relationship / Tumor Cells, Cultured
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0968-0896(01)00419-9
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11886804; ● Search Scopus @ Elsevier (PMID): 11886804; ● Search Scopus @ Elsevier (DOI): 10.1016/S0968-0896(01)00419-9

(DOI: 10.1016/S0968-0896(01)00419-9, PubMed: 11886804) Shinya Oishi, Takae Kamano, Ayumu Niida, Yoshihiko Odagaki, Hirokazu Tamamura, Akira Otaka, Nobuyuki Hamanaka and Nobutaka Fujii :
Diastereoselective synthesis of psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type dipeptide isosteres by organocopper-mediated anti-S(N)2' reaction,
Organic Letters, Vol.4, No.7, 1051-1054, 2002.

(要約): [reaction: see text] Acyclic psi[(E)-CH=CMe]- and psi[(Z)-CH=CMe]-type dipeptide isosteres were efficiently synthesized. In a key reaction, alpha-alkylation of gamma-mesyloxy-beta-methyl-alpha,beta-unsaturated esters with organocyanocuprates in diethyl ether or tetrahydrofuran preferentially afforded the psi[(E)-CH=CMe]- or psi[(Z)-CH=CMe]-isomer, respectively, via anti-S(N)2' mechanism.
(キーワード): Alkylation / Copper / Dipeptides / Indicators and Reagents / Organometallic Compounds / Stereoisomerism
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/ol016834j
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11922780; ● Search Scopus @ Elsevier (PMID): 11922780; ● Search Scopus @ Elsevier (DOI): 10.1021/ol016834j

(DOI: 10.1021/ol016834j, PubMed: 11922780) Shinya Oishi, Ayumu Niida, Takae Kamano, Yoshihiko Odagaki, Hirokazu Tamamura, Akira Otaka, Nobuyuki Hamanaka and Nobutaka Fujii :
Diastereoselective synthesis of psi[(E)-CMe=CH]- and psi[(E)-CMe=CMe]- type dipeptide isosteres based on organocopper-mediated anti-S(N)2' reaction,
Organic Letters, Vol.4, No.7, 1055-1058, 2002.

(要約): [reaction: see text] A straightforward synthetic route for the synthesis of diastereomerically pure psi[(E)-CMe=CH]- and psi[(E)-CMe=CMe]-type dipeptide isosteres was developed on the basis of regio- and stereoselective anti-S(N)2' alkylation of 3-(N-Boc-5-methyl-4-substituted-oxazolidin-2-on-5-yl)acrylates with organocopper reagents.
(キーワード): Alkylation / Copper / Dipeptides / Indicators and Reagents / Organometallic Compounds / Stereoisomerism
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/ol016835b
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11922781; ● Search Scopus @ Elsevier (PMID): 11922781; ● Search Scopus @ Elsevier (DOI): 10.1021/ol016835b

(DOI: 10.1021/ol016835b, PubMed: 11922781) Ryo Hosotani, Yoshiharu Miyamoto, Koji Fujimoto, Ryuichiro Doi, Akira Otaka, Nobutaka Fujii and Masayuki Imamura :
Trojan p16 Peptide Suppresses Pancreatic Cancer Growth and Prolongs Survival in Mice,
Clinical Cancer Research, Vol.8, No.4, 1271-1276, 2002.

(要約): The tumor suppressor gene p16INK4A is inactivated frequently in a large number of human cancers, and many investigators have attempted to restore the function of p16 using the p16 wild-type gene and viral vectors. In this study, we treated the tumor-bearing animals with the p16-derived synthetic peptide coupled with the Antennapedia carrier sequence, which we designated as Trojan p16 peptide. Injections (i.p.) of the Trojan p16 peptide (100 microg/mouse/day) were given for 3 weeks in the AsPC-1 and BxPC-3 s.c. tumor models. Tumor growth, histopathology, and TUNEL staining of the tumor and toxicity of the animals were evaluated. To examine its influence on the survival of tumor-bearing mice, Trojan p16 was administered in the AsPC-1 peritoneal dissemination model. In the AsPC-1 s.c. tumor model, a significant growth inhibition was obtained by the Trojan p16 treatment when compared with the three control treatments, i.e., vehicle, unconjugated form of p16, or Trojan peptide alone. Tumor growth inhibition was almost complete in the BxPC-3 tumor, a relatively slow growing tumor. Neither hematological cytotoxicity or body weight loss were observed. Histopathology of the BxPC-3 s.c. tumor in the Trojan p16 treatment group revealed marked vacuole formation and apoptotic death of cancer cells. In the AsPC-1 peritoneal dissemination model, the survival curve of mice treated with Trojan p16 was significantly longer than that of control. These results provide evidence that the Trojan p16 peptide system, a gene-oriented peptide coupled with a peptide vector, functions for experimental pancreatic cancer therapy.
(キーワード): Amino Acid Sequence / Animals / Blood Cell Count / Body Weight / Cell Division / Cyclin-Dependent Kinase Inhibitor p16 / Dose-Response Relationship, Drug / Humans / Male / Mice / Mice, Inbred BALB C / Mice, Nude / Molecular Sequence Data / Neoplasm Transplantation / Pancreatic Neoplasms / Peptide Fragments / Survival Analysis / Survival Rate / Tumor Cells, Cultured / Xenograft Model Antitumor Assays
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11948142; ● Search Scopus @ Elsevier (PMID): 11948142

(PubMed: 11948142) Hirokazu Tamamura, Kenichi Hiramatsu, Kazuhide Miyamoto, Akane Omagari, Shinya Oishi, Hideki Nakashima, Naoki Yamamoto, Yoshihiro Kuroda, Terumichi Nakagawa, Akira Otaka and Nobutaka Fujii :
Synthesis and evaluation of pseudopeptide analogues of a specific CXCR4 inhibitor, T140: The insertion of an (E)-alkene dipeptide isostere into the βII' -turn moiety,
Bioorganic & Medicinal Chemistry Letters, Vol.12, No.6, 923-928, 2002.

(要約): A 14-residue peptide, T140, strongly inhibits the T-cell line-tropic HIV-1 (X4-HIV-1) infection, since this peptide functions as a specific antagonist against a chemokine receptor, CXCR4. T140 takes an antiparallel beta-sheet structure with a type II' beta-turn. In the present paper, we have designed and synthesized several T140 analogues, in which an (E)-alkene dipeptide isostere was inserted into the type II' beta-turn moiety, as a bridging study to develop nonpeptidic CXCR4 inhibitors. It has been proven that the turn region of T140 can be replaced by the above surrogate with the maintenance of strong anti-HIV activity.
(キーワード): Anti-HIV Agents / Calcium Signaling / Cell Division / Dipeptides / HIV-1 / Humans / Inhibitory Concentration 50 / Microbial Sensitivity Tests / Models, Molecular / Oligopeptides / Protein Structure, Secondary / Receptors, CXCR4 / Tumor Cells, Cultured
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0960-894X(02)00041-0
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11958995; ● Summary page in Scopus @ Elsevier: 2-s2.0-18344368807

(DOI: 10.1016/S0960-894X(02)00041-0, PubMed: 11958995, Elsevier: Scopus) Yoshihito Taniguchi, Helena Karlström, Johan Lundkvist, Tomohiko Mizutani, Akira Otaka, Monica Vestling, Alan Bernstein, Dorit Donoviel, Urban Lendahl and Tasuku Honjo :
Notch receptor cleavage depends on but is not directly executed by presenilins,
Proceedings of the National Academy of Sciences of the United States of America, Vol.99, No.6, 4014-4019, 2002.

(出版サイトへのリンク): ● Publication site (DOI): 10.1073/pnas.052017699
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1073/pnas.052017699

(DOI: 10.1073/pnas.052017699) Shinya Oishi, Ayumu Niida, Takae Kamano, Yoshihisa Miwa, Tooru Taga, Yoshihiko Odagaki, Nobuyuki Hamanaka, Mikio Yamamoto, Keiichi Ajito, Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Regio- and stereoselective ring-opening of chiral 1,3-oxazolidin-2-one derivatives by organocopper reagents provides novel access to di-, tri- and tetra-substituted alkene dipeptide isosteres,
Journal of the Chemical Society, Perkin Transactions 1, 1786-1793, 2002.

(出版サイトへのリンク): ● Publication site (DOI): 10.1039/b203482d
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-0035995712

(DOI: 10.1039/b203482d, Elsevier: Scopus) Hirokazu Tamamura, Tadakazu Hori, Akira Otaka and Nobutaka Fujii :
Efficient stereoselective synthesis of peptidomimetics containing hydroxyethylamine dipeptide isosteres utilizing the aza-Payne rearrangement and O, N-acyl transfer reactions,
Journal of the Chemical Society, Perkin Transactions 1, Vol.5, 577-580, 2002.

(出版サイトへのリンク): ● Publication site (DOI): 10.1039/B200324B
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-0036006409

(DOI: 10.1039/B200324B, Elsevier: Scopus) Toshiaki Hara, Yasuyuki Mitani, Kyoko Tanaka, Natsuko Uematsu, Asako Takakura, Tomoya Tachi, Hiroaki Kodama, Michio Kondo, Harumi Mori, Akira Otaka, Nobutaka Fujii and Katsumi Matsuzaki :
Heterodimer Formation between the Antimicrobial Peptides Magainin 2 and PGLa in Lipid Bilayers: A Cross-Linking Study,
Biochemistry, Vol.40, No.41, 12395-12399, 2001.

(要約): The antimicrobial peptides magainin 2 and PGLa, isolated from the skin of the African clawed frog Xenopus laevis, show marked synergism [Westerhoff, H. V., Zasloff, M., Rosner, J. L., Hendler, R. W., de Waal, A., Vaz Gomes, A., Jongsma, A. P. M., Riethorst, A., and Juretic, D. (1995) Eur. J. Biochem. 228, 257-264]. We suggested previously that these peptides form a potent heterodimer composed of either parallel or antiparallel helices in membranes [Matsuzaki, K., Mitani, Y., Akada, K., Murase, O., Yoneyama, S., Zasloff, M., and Miyajima, K. (1998) Biochemistry 37, 15144-15153]. To detect the putative heterodimer by chemical cross-linking, analogues of magainin 2 and PGLa with a Cys residue at either terminus were synthesized. These cross-linking experiments suggested that both peptides form a parallel heterodimer in membranes composed of phosphatidylglycerol/phosphatidylcholine but not in either buffer or a helix-promoting 2,2,2-trifluoroethanol/buffer mixture. The isolated parallel heterodimers exhibited an order of magnitude higher membrane permeabilization activity compared with the monomeric species, indicating that the observed synergism is due to heterodimer formation.
(キーワード): Amino Acid Sequence / Animals / Antimicrobial Cationic Peptides / Cross-Linking Reagents / Dimerization / Drug Design / Drug Synergism / In Vitro Techniques / Lipid Bilayers / Magainins / Molecular Sequence Data / Permeability / Protein Precursors / Xenopus Proteins / Xenopus laevis
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/bi011413v
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11591159; ● Search Scopus @ Elsevier (PMID): 11591159; ● Search Scopus @ Elsevier (DOI): 10.1021/bi011413v

(DOI: 10.1021/bi011413v, PubMed: 11591159) Akira Otaka, Hideaki Watanabe, Akira Yukimasa, Shinya Oishi, Hirokazu Tamamura and Nobutaka Fujii :
New access to α-substituted (Z)-fluoroalkene dipeptide isosteres utilizing organocopper reagents under `reduction oxidative alkylation (R-OA)' conditions,
Tetrahedron Letters, Vol.42, No.32, 5443-5446, 2001.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0040-4039(01)01010-3
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-0035817225

(DOI: 10.1016/S0040-4039(01)01010-3, Elsevier: Scopus) Hirokazu Tamamura, Akane Omagari, Kenichi Hiramatsu, Taisei Kanamoto, Kazuyo Gotoh, Kenji Kanbara, Naoki Yamamoto, Hideki Nakashima, Akira Otaka and Nobutaka Fujii :
Synthesis and evaluation of bifunctional anti-HIV agents based on specific CXCR4 antagonists-AZT conjugation,
Bioorganic & Medicinal Chemistry, Vol.9, No.8, 2179-2187, 2001.

(要約): We have previously found that T140, a 14-amino acid residue peptide, inhibits infection of target cells by T cell-line-tropic strains of HIV-1 (X4-HIV-1) through its specific binding to a chemokine receptor, CXCR4. Here, we report synthesis and evaluation of bifunctional anti-HIV compounds, which are composed of T140 analogues and a reverse transcriptase inhibitor, 3'-azido-3'-deoxythymidine (AZT). Novel conjugated analogues have been proved to have the ability for controlled release of AZT in neutral aqueous media as well as mouse and feline sera, and high selectivity indexes (SIs, 50% cytotoxic concentration/50% effective concentration) caused by a synergistic effect of two different regenerating agents. Thus, these bifunctional compounds have several potential advantages. T140 analogues can possibly work as a carrier of AZT targeting T cells due to their specific affinity for CXCR4 on T cells. A synergistic effect by two types of regenerating agents may enable drug dosage to be reduced, and thus it may effectively suppress toxic side effects and the appearance of drug-resistant virus.
(キーワード): Animals / Anti-HIV Agents / Cats / Drug Stability / HIV-1 / Half-Life / Humans / Immune Sera / Mice / Receptors, CXCR4 / Tumor Cells, Cultured / Zidovudine
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0968-0896(01)00128-6
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11504655; ● Summary page in Scopus @ Elsevier: 2-s2.0-0034907536

(DOI: 10.1016/S0968-0896(01)00128-6, PubMed: 11504655, Elsevier: Scopus) Hirokazu Tamamura, Akane Omagari, Kenichi Hiramatsu, Kazuyo Gotoh, Taisei Kanamoto, Younong Xu, Eiichi Kodama, Masao Matsuoka, Toshio Hattori, Naoki Yamamoto, Hideki Nakashima, Akira Otaka and Nobutaka Fujii :
Development of specific CXCR4 inhibitors possessing high selectivity indexes as well as complete stability in serum based on an anti-HIV peptide T140,
Bioorganic & Medicinal Chemistry Letters, Vol.11, No.14, 1897-1902, 2001.

(要約): We previously reported a truncated polyphemusin peptide analogue, T140, which efficiently inhibits infection of target cells by T-cell line-tropic strains of HIV-1 (X4-HIV-1) through its specific binding to a chemokine receptor, CXCR4. We have found that T140 is not stable in feline serum due to the cleavage of the C-terminal Arg,(14) indispensable for anti-HIV activity. On the other hand, a C-terminally amidated analogue of T140, TZ14004, has been found to be completely stable in incubation in the serum for 2 days. The C-terminal amide is thought to be needed for stability in serum. However, TZ14004 does not have fairly strong anti-HIV activity, but has relatively strong cytotoxicity, probably due to an increase by +1 charge from total +7 charges of T140. In our previous study, the number of total +6 charges seemed to be a suitable balance between activity and cytotoxicity. In this study, we have conducted a double-L-citrulline (Cit)-scanning study on TZ14004 based on the C-terminally amidated form in due consideration of the total net charges in the whole molecule to find novel effective CXCR4 inhibitors, TN14003 ([Cit(6)]-T140 with the C-terminal amide) and TC14012 ([Cit(6), D-Cit(8)]-T140 with the C-terminal amide), which possess high selectivity indexes (SIs) and complete stability in feline serum.
(キーワード): Animals / Anti-HIV Agents / Cats / Cell Survival / Circular Dichroism / Citrulline / Drug Stability / HIV-1 / Humans / Inhibitory Concentration 50 / Oligopeptides / Peptides / Receptors, CXCR4
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0960-894X(01)00323-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11459656; ● Summary page in Scopus @ Elsevier: 2-s2.0-0035939252

(DOI: 10.1016/S0960-894X(01)00323-7, PubMed: 11459656, Elsevier: Scopus) Terrence R Burke-Jr, Jun-Zhu Yao, Bin Ye, Kengo Miyoshi, Akira Otaka, Li Wu and Zhong-Yin Zhang :
Phospho-azatyrosine, a less effective protein-tyrosine phosphatase substrate than phosphotyrosine,
Bioorganic & Medicinal Chemistry Letters, Vol.11, No.10, 1265-1268, 2001.

(要約): Azatyrosine (AzaTyr, 4) is a natural product isolated from Streptomyces chibanesis, whose structure is characterized by a nitrogen atom in the aryl ring of a tyrosyl residue. This seemingly minor modification to the tyrosyl residue results in profound physiological effects, as AzaTyr has been shown to promote permanent reversion of ras-dependent transformed cells to the normal phenotype in culture and to inhibit chemical induction of carcinogenesis in transgenic mice bearing oncogenic human ras. The mechanisms underlying these effects are not known, however ras-pathways involve an intricate balance between both protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). The present study was undertaken to examine the general utility of AzaTyr as a structural motif for PTP inhibitor design by examining the phospho-azatyrosine (pAzaTyr)-containing peptide Ac-Asp-Ala-Asp-Glu-pAzaTyr-Leu-amide (8) in a PTP1 enzyme system. Kinetic analysis indicated that 8 binds with a Km value of 210 microM and a catalytic turnover rate, kcat of 52 s(-1). This represents a greater than 50-fold reduction in binding affinity relative to the parent phosphotyrosine-containing peptide, indicating that the aryl nitrogen adversely affects binding affinity. The much lower PTP affinity of the pAzaTyr-containing peptide reduces the potential utility of the AzaTyr pharmacophore for PTP inhibitor design. These results are discussed from the point of view that incorporation of AzaTyr residues into proteins could result in perturbation of protein-tyrosine phosphorylation,dephosphorylation cascades that control signal transduction processes, including ras-dependent pathways.
(キーワード): Alanine / Animals / Anticarcinogenic Agents / Catalytic Domain / Drug Design / Enzyme Inhibitors / Humans / Kinetics / Molecular Mimicry / Peptides / Phosphotyrosine / Protein Tyrosine Phosphatases / Structure-Activity Relationship / Substrate Specificity
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0960-894X(01)00197-4
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11392533; ● Summary page in Scopus @ Elsevier: 2-s2.0-0342960996

(DOI: 10.1016/S0960-894X(01)00197-4, PubMed: 11392533, Elsevier: Scopus) Hirokazu Tamamura, Makiko Sugioka, Yoshihiko Odagaki, Akane Omagari, Yukiko Kan, Shinya Oishi, Hideki Nakashima, Naoki Yamamoto, Stephen C. Peiper, Nobuyuki Hamanaka, Akira Otaka and Nobutaka Fujii :
Conformational study of a highly specific CXCR4 inhibitor, T140, disclosing the close proximity of its intrinsic pharmacophores associated with strong anti-HIV activity,
Bioorganic & Medicinal Chemistry Letters, Vol.11, No.3, 359-362, 2001.

(要約): We report the solution structure of T140, a truncated polyphemusin peptide analogue that efficiently inhibits infection of target cells by T-cell line-tropic strains of HIV-1 through its specific binding to a chemokine receptor, CXCR4. Nuclear magnetic resonance analysis and molecular dynamic calculations revealed that T140 has a rigidly structured conformation constituted by an antiparallel beta-sheet and a type II' beta-turn. A protuberance is formed on one side of the beta-sheet by the side-chain functional groups of the three amino acid residues (L-3-(2-naphthyl)alanine, Tyr5 and Arg14), each of which is indispensable for strong anti-HIV activity. These findings provide a rationale to dissect the structural basis for the ability of this compound to block the interaction between CXCR4 and envelope glycoproteins from T-tropic strains of HIV-1.
(キーワード): Amino Acid Sequence / Anti-HIV Agents / Computer Simulation / Models, Molecular / Molecular Conformation / Nuclear Magnetic Resonance, Biomolecular / Oligopeptides / Protein Structure, Secondary / Receptors, CXCR4 / Structure-Activity Relationship
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0960-894X(00)00664-8
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11212110; ● Summary page in Scopus @ Elsevier: 2-s2.0-0035847678

(DOI: 10.1016/S0960-894X(00)00664-8, PubMed: 11212110, Elsevier: Scopus) Akira Otaka, Hideaki Watanabe, Etsuko Mitsuyama, Akira Yukimasa, Hirokazu Tamamura and Nobutaka Fujii :
Synthesis of (Z)-fluoroalkene dipeptide isosteres utilizing organocopper-mediated reduction of γ,γ-difluoro-α,β-enoates,
Tetrahedron Letters, Vol.42, No.2, 285-287, 2001.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0040-4039(00)01924-9
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-0035825087

(DOI: 10.1016/S0040-4039(00)01924-9, Elsevier: Scopus) Shinya Oishi, Hirokazu Tamamura, Masaki Yamashita, Yoshihiko Odagaki, Nobuyuki Hamanaka, Akira Otaka and Nobutaka Fujii :
Stereoselective synthesis of a set of two functionalized (E)-alkene dipeptide isosteres of L-amino acid-L-Glu and L-amino acid-D-Glu,
Journal of the Chemical Society, Perkin Transactions 1, 2445-2451, 2001.

(出版サイトへのリンク): ● Publication site (DOI): 10.1039/B103833H
(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-0034740849

(DOI: 10.1039/B103833H, Elsevier: Scopus) Hirokazu Tamamura, Akane Omagari, Shinya Oishi, Taisei Kanamoto, Naoki Yamamoto, Stephen C. Peiper, Hideki Nakashima, Akira Otaka and Nobutaka Fujii :
Pharmacophore identification of a specific CXCR4 inhibitor, T140, leads to development of effective anti-HIV agents with very high selectivity indexes,
Bioorganic & Medicinal Chemistry Letters, Vol.10, No.23, 2633-2637, 2000.

(要約): A polyphemusin peptide analogue, T22 ([Tyr(5,12), Lys7]-polyphemusin II), and its shortened potent analogues, T134 (des-[Cys(8,13), Tyr(9,12)]-[D-Lys10, Pro11, L-citrulline16]-T22 without C-terminal amide) and T140 [[L-3-(2-naphthyl)alanine3]-T134], strongly inhibit the T-cell line-tropic (T-tropic) HIV-1 infection through their specific binding to a chemokine receptor, CXCR4. T22 is an extremely basic peptide possessing five Arg and three Lys residues in the molecule. In our previous study, we found that there is an apparent correlation in the T22-related peptides between the number of total positive charges and anti-HIV activity or cytotoxicity. Here, we have conducted the conventional Ala-scanning study in order to define the anti-HIV activity pharmacophore of T140 (the strongest analogue among our compounds) and identified four indispensable amino acid residues (Arg2, Nal3, Tyr5, and Arg14). Based on this result, a series of L-citrulline (Cit)-substituted analogues of T140 with decreased net positive charges have been synthesized and evaluated in terms of anti-HIV activity and cytotoxicity. As a result, novel effective inhibitors, TC14003 and TC14005, possessing higher selectivity indexes (SIs, 50% cytotoxic concentration/50% effective concentration) than that of T140 have been developed.
(キーワード): Amino Acid Sequence / Anti-HIV Agents / Cell Line / Circular Dichroism / HIV-1 / Humans / Microbial Sensitivity Tests / Molecular Sequence Data / Oligopeptides / Receptors, CXCR4
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0960-894X(00)00535-7
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11128640; ● Summary page in Scopus @ Elsevier: 2-s2.0-0034606466

(DOI: 10.1016/S0960-894X(00)00535-7, PubMed: 11128640, Elsevier: Scopus) Koji Fujimoto, Ryo Hosotani, Yoshiharu Miyamoto, Ryuichiro Doi, Takatomo Koshiba, Akira Otaka, Nobutaka Fujii, Robert D. Beauchamp and Masayuki Imamura :
Inhibition of pRb phosphorylation and cell cycle progression by an antennapedia-p16(INK4A) fusion peptide in pancreatic cancer cells,
Cancer Letters, Vol.159, No.2, 151-158, 2000. Yoshimi Sagawa, Yoshiyuki Yoshimura, Akira Otaka and Takashi Yamauchi :
Ca²⁺-independent activity of Ca²⁺/calmodulin-dependent protein kinase II involved in stimulation of neurite outgrowth in neuroblastoma cells,
Brain Research, Vol.881, No.2, 165-175, 2000.

(要約): We investigated the involvement of Ca(2+)-independent activity of Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) in stimulation of neurite outgrowth. When neuroblastoma Neruo2a (Nb2a) cells expressing the alpha isoform of CaM kinase II (Nb2a/alpha cells) were stimulated by plating, they changed shape from round to flattened, and began to form neurites within 15 min. Numbers of cells bearing neurites increased from 15 min to about 2 h. Neurite length increased markedly from 30 min to 2 h after stimulation. Ca(2+)-independent activity of CaM kinase II increased immediately after stimulation, peaked at about 30 min, and then gradually decreased. Autophosphorylation of Thr-286 followed the same time course as the increase in Ca(2+)-independent activity. The autophosphorylation and appearance of Ca(2+)-independent activity preceded the formation of neurites. The effect of mutation of the autophosphorylation site in the kinase whose Thr-286 was replaced with Ala (alphaT286A kinase) or Asp (alphaT286D kinase) was examined. alphaT286A kinase was not converted to a Ca(2+)-independent form, and alphaT286D kinase had Ca(2+)-independent activity significantly as an autophosphorylated kinase. Cells expressing alphaT286A kinase did not form neurites, and were indistinguishable from control Nb2a cells. Cells expressing alphaT286D kinase had much longer neurites than Nb2a/alpha cells expressing the wild type kinase, although the initiation of neurite outgrowth was very late. These results indicated that Ca(2+)-independent activity of the kinase autophosphorylated at Thr-286 involves for neurite outgrowth.
(キーワード): Ca2+/calmodulin-dependent protein kinase II / Autophosphorylation / Neurite outgrowth / Ca2+-independent activity / Neuroblastoma
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0006-8993(00)02838-9
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11036155; ● Summary page in Scopus @ Elsevier: 2-s2.0-0034722095

(DOI: 10.1016/S0006-8993(00)02838-9, PubMed: 11036155, Elsevier: Scopus) Yoshihiro Kuroda, Kazuhide Miyamoto, Kazufumi Tanaka, Yoshitaka Maeda, J Ishikawa, R Hinata, Akira Otaka, Nobutaka Fujii and Terumichi Nakagawa :
Interactions between Local Anesthetics and Na+ Channel Inactivation Gate Peptides in Phosphatidylserine Suspensions as Studied by 1H-NMR Spectroscopy,
Chemical & Pharmaceutical Bulletin, Vol.48, No.9, 1293-1298, 2000. Yoshihiro Kuroda, Kazuhide Miyamoto, M Matsumoto, Yishitaka Maeda, Kenji Kanaori, Akira Otaka, Nobutaka Fujii and Terumichi Nakagawa :
Structural study of the sodium channel inactivation gate peptide including an isoleucine-phenylalanine-methionine motif and its analogous peptide (phenylalanine/glutamine) in trifluoroethanol solutions and SDS micelles,
The Journal of Peptide Research, Vol.56, No.3, 172-184, 2000.

(要約): In order to gain insight into the gating mechanisms of Na+ channels, in particular their inactivation mechanisms, we studied the structures of the Na+ channel inactivation gate related peptide which includes the IFM (Ile-Phe-Met) motif (Ac-KKKFGGQDIFMTEEQKK-NH2; K1480-K1496 in rat brain type-IIA Na+ channels, MP-3A) and its F/Q(Gln) substituted one (MP-4A) in trifluoroethanol (TFE) solutions and sodium dodecyl sulfate (SDS) micelles using circular dichroism (CD) and 1H-NMR spectroscopies. Based on observed nuclear Overhauser effect constraints, three-dimensional structures of MP-3A and MP-4A were determined using simulated annealing molecular dynamics/ energy minimization calculations. In TFE solutions, no appreciable differences in the structure were observed using either CD or NMR spectra. In SDS micelles, however, the two peptides exhibited definitely different structures from each other. It was found that in MP-3A, residues 11488 and T1491 were spatially proximate with each other owing to hydrogen bonding between the amide proton of 11488 and the hydroxyl oxygen atom of T1491, whereas in MP-4A, F/Q substitution separated them owing to conformational changes. The solvent-accessible surfaces calculated for the structures of MP-3A and MP-4A showed that the former has a smoother interaction surface to the hydrophobic docking site than the latter. In conclusion, the conformational changes, as well as decreased hydrophobicity around the IFM motif owing to the F/Q mutation, may be one reason why F1489Q mutated channels cannot inactivate almost completely.
(キーワード): Amino Acid Motifs / Circular Dichroism / Ion Channel Gating / Isoleucine / Methionine / Nuclear Magnetic Resonance, Biomolecular / Oligopeptides / Peptide Fragments / Phenylalanine / Sodium Channel Blockers / Sodium Dodecyl Sulfate / Trifluoroethanol
(出版サイトへのリンク): ● Publication site (DOI): 10.1034/j.1399-3011.2000.00745.x
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11007274; ● Summary page in Scopus @ Elsevier: 2-s2.0-0033831716

(DOI: 10.1034/j.1399-3011.2000.00745.x, PubMed: 11007274, Elsevier: Scopus) Akira Otaka, Etsuko Mitsuyama, Takayoshi Kinoshita, Hirokazu Tamamura and Nobutaka Fujii :
Stereoselective Synthesis of CF₂-Substituted Phosphothreonine Mimetics and Their Incorporation into Peptides Using Newly Developed Deprotection Procedures,
The Journal of Organic Chemistry, Vol.65, No.16, 4888-4899, 2000.

(要約): Stereoselective syntheses of all four stereoisomers of CF(2)-substituted nonhydrolyzable phosphothreonine derivatives (33, 39, and their enantiomers) and their incorporation into peptides are described herein. Key to the synthesis of these amino acids was construction of secondary phosphate-mimicking difluoromethylphosphonate units along with generation of two stereocenters. The former was achieved using a Cu(I)-mediated cross-coupling reaction of BrZnCF(2)P(O)(OEt)(2) (8) and beta-iodo-alpha,beta-unsaturated ester 12, with stereochemistry of both alpha- and beta-stereocenters being established using bornane-10,2-sultam as a chiral auxiliary. Diastereoselective hydrogenation of a chiral alpha,beta-unsaturated acylsultam (for the beta-center) (e.g., 16a) and subsequent stereoselective bromination (for the alpha-center of the threo derivative) or amination (for the alpha-center of erythro (allo) derivative) were utilized. Transesterification of the bromide to the benzyl ester followed by azide displacement of the halogen, then reduction of the resulting azide, followed by Boc-protection and finally removal of the benzyl group, afforded protected both L- and D-phosphothreonine mimetics (39 and its enantiomer). On the other hand, protected both L- and D-allo-phosphothreonine mimetics (33 and its enantiomer) were synthesized via transesterification of the above-mentioned amination product, followed by hydrogenolytic removal of the benzyl group. Key to utilization of these amino acid analogues in peptide synthesis was removal of ethyl protection from the difluoromethylphosphonate moiety. A two-step deprotection methodology, consisting of a combination of a first-step reagent [0.3 M BSTFA-TBAI in CH(2)Cl(2), BF(3).Et(2)O] followed by a second-step reagent [1 M TMSOTf-thioanisole in TFA, m-cresol, EDT] was developed for use in solid-phase protocols. A 12-residue Cdc (cell division cycle) 2-peptide 41, possessing two nonhydrolyzable phosphoamino acid mimetics (F(2)Pmab 6 and F(2)Pmp 4), was subjected to this deprotection procedure and was obtained in 25% yield based on the protected resin. The present synthetic method affords nonhydrolyzable phosphoamino acid mimetics-containing peptides in high yield without accompanying side reactions.
(キーワード): Indicators and Reagents / Isomerism / Molecular Mimicry / Peptides / Phosphothreonine / Threonine
(出版サイトへのリンク): ● Publication site (DOI): 10.1021/jo000169v
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10956468; ● Summary page in Scopus @ Elsevier: 2-s2.0-0034637581

(DOI: 10.1021/jo000169v, PubMed: 10956468, Elsevier: Scopus) Kengo Miyoshi, Akira Otaka, Midori Kaneko, Hirokazu Tamamura and Nobutaka Fujii :
A New Practical Strategy for the Synthesis of Long-chain Phosphopeptide,
Chemical & Pharmaceutical Bulletin, Vol.48, No.88, 1230-1233, 2000.

(要約): A new practical strategy has been developed for the synthesis of long-chain phosphopeptide. Both the 2-chlorobenzyloxycarbonyl (CIZ) group for Lys and methyl (Me) for phosphoamino acids remained intact, while other commonly used side-chain protecting groups were cleaved quantitatively, during the reaction using a highly acidic trifluoromethanesulfonic acid (TFMSA)-based reagent system (High TFMSA: TFMSA-TFA-m-cresol=1:9:1, v/v). Selective deprotection of the CIZ and Me group-containing protected phosphopeptide resin with the High TFMSA gave a partially protected phosphopeptide fragment suitable for thioester-mediated fragment condensation. A deprotection protocol of the 9-fluorenylmethyloxycarbonyl (Fmoc) group, which evades significant side reaction toward the protected phosphoamino acid, was also developed. These two new findings enabled us to synthesize long-chain phosphopeptide via thioester-mediated fragment condensation.
(キーワード): Amino Acid Sequence / Esters / Molecular Sequence Data / Phosphopeptides
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10959596; ● Summary page in Scopus @ Elsevier: 2-s2.0-0033840114

(PubMed: 10959596, Elsevier: Scopus) Motoyoshi Nomizu, Yuichiro Kuratomi, M. Lourdes Ponce, Sang Yong Song, Kengo Miyoshi, Akira Otaka, Sharon K. Powell, Matthew P. Hoffman, Hynda K. Kleinman and Yoshihiko Yamada :
Cell Adhesive Sequences in Mouse Laminin β1 Chain,
Archives of Biochemistry and Biophysics, Vol.378, No.2, 311-320, 2000.

(要約): Laminin-1, a major component of the basement membrane, consists of three different chains, alpha1, beta1, and gamma1. We sought to identify cell adhesive sequences from the mouse laminin beta1 chain by testing HT-1080 fibrosarcoma and B16-F10 melanoma cells for binding to 187 overlapping synthetic peptides which covered the entire chain. Fourteen peptides showed cell adhesive activities with either peptide-conjugated Sepharose beads or peptide-coated plates or both. Additional cells, including neuronal, endothelial, and salivary gland cells, showed biological responses in a cell type-specific manner. B-7, B-133, and B-160 showed the most potent cell attachment. Cell binding on three peptides (B-34, B-133, and B-160) was inhibited by EDTA. Cell adhesion to 11 of the 12 active peptides was inhibited to varying degrees by heparin. Of the 17 active peptides identified in the laminin beta1 chain in this and other studies, 8 are clustered on the amino terminal globular domain, suggesting a possible important role in cell binding for this domain that may be multifunctional. These data demonstrate that the laminin beta1 chain has multiple active sites for cell adhesion, some of which are cell-type specific.
(キーワード): Amino Acid Sequence / Animals / Cell Adhesion / Cell Line / Cells, Cultured / Dose-Response Relationship, Drug / Edetic Acid / Endothelium, Vascular / Fibrinolytic Agents / Heparin / Humans / Laminin / Mice / Models, Biological / Molecular Sequence Data / Peptides / Protein Binding / Rats / Sepharose / Sequence Homology, Amino Acid / Tumor Cells, Cultured
(出版サイトへのリンク): ● Publication site (DOI): 10.1006/abbi.2000.1828
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10860548; ● Summary page in Scopus @ Elsevier: 2-s2.0-0034660312

(DOI: 10.1006/abbi.2000.1828, PubMed: 10860548, Elsevier: Scopus) Akira Otaka, Etsuko Mitsuyama, Hideaki Watanabe, Hirokazu Tamamura and Nobutaka Fujii :
Development of new methodology for the synthesis of functionalized α-fluorophosphonates and its practical application to the preparation of phosphopeptide mimetics,
Chemical Communications, 1081-1082, 2000.

(文献検索サイトへのリンク): ● Summary page in Scopus @ Elsevier: 2-s2.0-0034697761

(Elsevier: Scopus) Yoshihiro Kuroda, Yoshitaka Maeda, Kazuhide Miyamoto, Kazufumi Tanaka, Kenji Kanaori, Akira Otaka, Nobutaka Fujii and Terumichi Nakagawa :
1H-NMR and Circular Dichroism Spectroscopic Studies on Changes in Secondary Structures of the Sodium Channel Inactivation Gate Peptides as Caused by the Pentapeptide KIFMK,
Biophysical Journal, Vol.77, No.3, 1363-1373, 1999. Hirokazu Tamamura, Masaki Yamashita, Yutaka Nakajima, Kyoko Sakano, Akira Otaka, Hiroaki Ohno, Toshiro Ibuka and Nobutaka Fujii :
Regiospecific ring-opening reactions of β-aziridinyl α,β-enoates with acids: application to the stereoselective synthesis of a couple of diastereoisomeric (E)-alkene dipeptide isosteres from a single β-aziridinyl α,β-enoate and to the convenient preparation of amino alcohols bearing α,β-unsaturated ester groups,
Journal of the Chemical Society, Perkin Transactions 1, 2983-2996, 1999. Shunji Kanaoka, Seiji Yamasaki, Takashi Okino, Naoya Inoue, Yutaka Shimada, Midori Kaneko, Akira Otaka, Nobutaka Fujii and Masayuki Imamura :
Induction of human leukocyte antigen (HLA)-A2-restricted and MAGE-3-gene-derived peptide-specific cytolytic T lymphocytes using cultured dendritic cells from an HLA-A2 esophageal cancer patient,
Journal of Surgical Oncology, Vol.71, No.1, 16-21, 1999. Hirokazu Tamamura, Younong Xu, Toshio Hattori, Xiaoyan Zhang, Rieko Arakaki, Kenji Kanbara, Akane Omagari, Akira Otaka, Toshiro Ibuka, Naoki Yamamoto, Hideki Nakashima and Nobutaka Fujii :
A Low-Molecular-Weight Inhibitor against the Chemokine Receptor CXCR4: A Strong Anti-HIV Peptide T140,
Biochemical and Biophysical Research Communications, Vol.253, No.3, 877-882, 1998.

(要約): T22 ([Tyr5,12, Lys7]-polyphemusin II) is an 18-residue peptide amide, which has strong anti-HIV activity. T22 inhibits the T cell line-tropic (T-tropic) HIV-1 infection through its specific binding to a chemokine receptor CXCR4, which serves as a coreceptor for the entry of T-tropic HIV-1 strains. Herein, we report our finding of novel 14-residue CXCR4 inhibitors, T134 and T140, on the basis of the T22 structure. In the assays we examined, T140 showed the highest inhibitory activity against HIV-1 entry and the strongest inhibitory effect on the binding of an anti-CXCR4 monoclonal antibody (12G5) to CXCR4 among all the CXCR4 inhibitors that have been reported up to now.
(キーワード): Amino Acid Sequence / Anti-HIV Agents / Antimicrobial Cationic Peptides / Cells, Cultured / Chemokine CXCL12 / Chemokines, CXC / Circular Dichroism / DNA-Binding Proteins / HIV-1 / Heterocyclic Compounds / Molecular Sequence Data / Oligopeptides / Peptides / Peptides, Cyclic / Receptors, CXCR4 / T-Lymphocytes
(出版サイトへのリンク): ● Publication site (DOI): 10.1006/bbrc.1998.9871
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 9918823; ● Summary page in Scopus @ Elsevier: 2-s2.0-0032583575

(DOI: 10.1006/bbrc.1998.9871, PubMed: 9918823, Elsevier: Scopus) Motoyoshi Nomizu, Yuichiro Kuratomi, Katherine M. Malinda, Sang Yong Song, Kengo Miyoshi, Akira Otaka, Sharon K. Powell, Matthew P. Hoffman, Hynda K. Kleinman and Yoshihiko Yamada :
Cell Binding Sequences in Mouse Laminin 1 Chain,
The Journal of Biological Chemistry, Vol.273, No.49, 32491-32499, 1998. Hirokazu Tamamura, Makoto Imai, Tsunehito Ishihara, Masao Masuda, Hanae Funakoshi, Hiromi Oyake, Tsutomu Murakami, Rieko Arakaki, Hideki Nakashima, Akira Otaka, Toshiro Ibuka, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Pharmacophore identification of a chemokine receptor (CXCR4) antagonist, T22 ([Tyr5,12, Lys7]-polyphemusin II), which specifically blocks T cell-line-tropic HIV-1 infection,
Bioorganic & Medicinal Chemistry, Vol.6, No.7, 1033-1041, 1998. Hirokazu Tamamura, Michinori Waki, Makoto Imai, Akira Otaka, Toshiro Ibuka, Koji Waki, Kenji Miyamoto, Akiyoshi Matsumoto, Tsutomu Murakami, Hideki Nakashima, Naoki Yamamoto and Nobutaka Fujii :
Downsizing of an HIV cell fusion inhibitor, T22 ([Tyr5,12, Lys7]-Polyphemusin II), with the maintenance of anti-HIV activity and solution structure,
Bioorganic & Medicinal Chemistry, Vol.6, No.4, 473-479, 1998. Hirokazu Tamamura, Rieko Arakaki, Hanae Funakoshi, Makoto Imai, Akira Otaka, Toshiro Ibuka, Hideki Nakashima, Tsutomu Murakami, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Effective lowly cytotoxic analogs of an HIV-cell fusion inhibitor, T22 ([Tyr5,12, Lys7]-polyphemusin II),
Bioorganic & Medicinal Chemistry, Vol.6, No.2, 231-238, 1998. Atsushi Kosaki, Kazunori Yamada, Junko Suga, Akira Otaka and Hideshi Kuzuya :
14-3-3β Protein Associates with Insulin Receptor Substrate 1 and Decreases Insulin-stimulated Phosphatidylinositol 3-Kinase Activity in 3T3L1 Adipocytes,
The Journal of Biological Chemistry, Vol.273, No.2, 940-944, 1998. Hirokazu Tamamura, F Matsumoto, Kyoko Sakano, Akira Otaka, Toshiro Ibuka and Nobutaka Fujii :
Unambiguous Synthesis of Stromal Cell-derived Factor-1 by Regioselective Disulfide Bond Formation Using a DMSO-aqueous HCl System,
Chemical Communications, No.1, 151-152, 1998. Hirokazu Tamamura, Tsunehito Ishihara, Hiromi Oyake, Makoto Imai, Akira Otaka, Toshiro Ibuka, Rieko Arakaki, Hideki Nakashima, Tsutomu Murakami, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Convenient one-pot synthesis of cystine-containing peptides using the trimethylsilyl chloride dimethyl sulfoxide/trifluoroacetic acid system and its application to the synthesis of bifunctional anti-HIV compounds1,
Journal of the Chemical Society, Perkin Transactions 1, 495-500, 1998. Motoyoshi Nomizu, Yuichiro Kuratomi, Sang-Yong Song, M. Lourdes Ponce, Matthew P. Hoffman, Sharon K. Powell, Kengo Miyoshi, Akira Otaka, Hynda K. Kleinman and Yoshihiko Yamada :
Identification of Cell Binding Sequences in Mouse Laminin 1 Chain by Systematic Peptide Screening,
The Journal of Biological Chemistry, Vol.272, No.51, 32198-32205, 1997. Hiroshi Aoyama, Norio Mimura, Hiroaki Ohno, Kiyonori Ishii, Ayako Toda, Hirokazu Tamamura, Akira Otaka, Nobutaka Fujii and Toshiro Ibuka :
Regio- and stereoselectivity in reactions of 2,3-cis- and trans-3-alkyl-2-vinylaziridines with organocopper reagents: Importance of 2,3-cis-stereochemistry in controlling selectivity,
Tetrahedron Letters, Vol.38, No.42, 7383-7386, 1997. Hiroaki Ohno, Norio Mimura, Akira Otaka, Hirokazu Tamamura, Nobutaka Fujii, Toshiro Ibuka, Isao Shimizu, Akiharu Satake and Yoshinori Yamamoto :
Palladium-Catalyzed Reductive Ring Opening with Formic Acid of Aziridines Bearing an α,β-Unsaturated Ester Group,
Tetrahedron, Vol.53, No.38, 12933-12946, 1997.

(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0040-4020(97)00817-X
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1016/S0040-4020(97)00817-X

(DOI: 10.1016/S0040-4020(97)00817-X) Hirokazu Tamamura, Masaki Yamashita, Hiroyuki Muramatsu, Hiroaki Ohno, Tohiro Ibuka, Akira Otaka and Nobutaka Fujii :
Regiospecific ring-opening reactions of aziridines bearing an α,β-unsaturated ester group with trifluoroacetic acid or methanesulfonic acid: application to the stereoselective synthesis of (E)-alkene dipeptide isosteres,
Chemical Communications, 2327-2328, 1997. Hirokazu Tamamura, Akira Otaka, Tsutomu Murakami, Toshiro Ibuka, Kyoko Sakano, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
An Anti-HIV Peptide, T22, Forms a Highly Active Complex with Zn(II),
Biochemical and Biophysical Research Communications, Vol.229, No.2, 648-652, 1996. Hirokazu Tamamura, Tsunehito Ishihara, Akira Otaka, Tsutomu Murakami, Toshiro Ibuka, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Analysis of the interaction of an anti-HIV peptide, T22 ([Tyr5, 12, Lys7]-polyphemusin II), with gp120 and CD4 by surface plasmon resonance,
Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, Vol.1298, No.1, 37-44, 1996.

(要約): We have previously found that T22 ([Tyr5, 12, Lys7]-polyphemusin II) exhibits strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2', 3'-dideoxythymidine (AZT). The inhibition mechanism of T22 on HIV-replication has not been elucidated precisely yet, and hence the target molecules of T22 have not been identified. However, our recent research suggested that T22 exerts its effect by blocking virus-cell fusion at an early stage of HIV infection and that T22 might interact with an HIV envelope protein and/or a T-cell surface protein, both of which are critical for HIV infection. In this paper we demonstrated that T22 binds specifically to both gp120 (an envelope protein of HIV) and CD4 (a T-cell surface protein) and that both bindings can be inhibited by an anti-T22 antibody, using biosensor technology (BIAcoreTM) based on the principles of surface plasmon resonance. Linearization by the BIAcoreTM system (BIAlogue software) and nonlinear least squares analysis by curve fitting with exponential equations showed that both interactions have close dissociation constants (approximately 10(-7) M). The present study suggests that T22 inhibits the virus-cell fusion process through binding to both gp120 and CD4.
(キーワード): Amino Acid Sequence / Anti-HIV Agents / Antibodies / Antigens, CD4 / Antimicrobial Cationic Peptides / Biosensing Techniques / HIV / HIV Envelope Protein gp120 / Kinetics / Membrane Fusion / Membrane Proteins / Molecular Sequence Data / Peptides / Protein Binding
(出版サイトへのリンク): ● Publication site (DOI): 10.1016/S0167-4838(96)00113-6
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8948487; ● Search Scopus @ Elsevier (PMID): 8948487; ● Search Scopus @ Elsevier (DOI): 10.1016/S0167-4838(96)00113-6

(DOI: 10.1016/S0167-4838(96)00113-6, PubMed: 8948487) Motoyoshi Nomizu, Atsushi Utani, Konrad Beck, Akira Otaka, Peter P. Roller and Akira Otaka :
Mechanism of Laminin Chain Assembly into a Triple-Stranded Coiled-Coil Structure,
Biochemistry, Vol.35, No.9, 2885-2893, 1996. Hirokazu Tamamura, Akira Otaka, Tsutomu Murakami, Tsunehito Ishihara, Toshiro Ibuka, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Interaction of an Anti-HIV Peptide, T22, with GP120 and CD4,
Biochemical and Biophysical Research Communications, Vol.219, No.2, 555-559, 1996. Joseph J. Barchi-Jr, Motoyoshi Nomizu, Akira Otaka, Peter P. Roller and Terrence R. Burke-Jr :
Conformational Analysis of Cyclic Hexapeptides Designed as Constrained Ligands for the SH2 Domain of the p85 Subunit of Phosphatidylinositol-3-OH Kinase.,
Biopolymers, Vol.38, No.2, 191-208, 1996.

(要約): The structures of the cyclic hexapeptide cyclo(-Gly-Tyr-Val-Pro-Met-Leu-) (1) and its phosphotyrosyl (pTyr) derivative cyclo[-Gly-Tyr(PO3H2)-Val-Pro-Met-Leu-] (2), designed as constrained models of a sequence that interacts with the src homology 2 (SH2) region of the p85 subunit of phosphatidylinositol-3-OH kinase (PI-3 kinase), were studied in methanol/water solutions by 500 MHz nmr spectroscopy. Compound 1 was found to exist as a 2:1 mixture of isomers about the Val-Pro bond (trans and cis prolyl) between 292-330 K in 75% CD3O(D,H)/(D,H)2O solutions. A third species of undetermined structure (ca. 5%) was also observed. Compound 2, a model of phosphorylated peptide ligand that binds to the PI-3 kinase SH2 domain, exhibited similar conformational isomerism. When either compound was dissolved in pure solvent [i.e., 100% CD3O(H,D) or (H,D)2O] the ratio of cis to trans isomers was ca 1:1. A battery of one- and two-dimensional nmr experiments at different temperatures and solvent compositions allowed a complete assignment of both the cis and trans forms of 1 and indicated the trans compound to be the major isomer. The spectral properties of the phophorylated derivative 2 paralleled those of 1, indicating like conformations for the two compounds. Analysis of rotating frame Overhauser spectroscopy data, coupling constants, amide proton temperature dependence, and amide proton exchange rates generated a set of constraints that were employed in energy minimization and molecular dynamics calculations using the CHARMM force field. The trans isomer exists with the tyrosine and C-terminal Tyr(+3) (Met) residues at opposite corners of the 18-membered ring separated by a distance of 16-18 A, in contrast with the cis isomer where the side chains of these residues are much closer in space (7-14 A). It was previously shown that the pTyr and the third amino acid C-terminal to this residue are the critical recognition elements for pTyr-peptide binding to the PI-3 kinase SH2 domain. Such cyclic structures may offer appropriate scaffolding for positioning important amino acid side chains of pTyr-containing peptides as a means of increasing their binding affinities to SH2 domains, and in turn provide a conceptual approach toward the design of SH2 domain directed peptidomimetics.
(キーワード): Amino Acid Sequence / Binding Sites / Ligands / Models, Molecular / Molecular Sequence Data / Oligopeptides / Peptides, Cyclic / Phosphatidylinositol 3-Kinases / Phosphotransferases (Alcohol Group Acceptor) / Protein Conformation / Thermodynamics / src Homology Domains
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/(SICI)1097-0282(199602)38:2<191::AID-BIP6>3.0.CO;2-Q
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 8589253; ● Search Scopus @ Elsevier (PMID): 8589253; ● Search Scopus @ Elsevier (DOI): 10.1002/(SICI)1097-0282(199602)38:2<191::AID-BIP6>3.0.CO;2-Q

(DOI: 10.1002/(SICI)1097-0282(199602)38:2<191::AID-BIP6>3.0.CO;2-Q, PubMed: 8589253) Bin Ye, Akira Otaka and Terrence R. Burke-Jr :
Preparation of Na-Boc 4-O-Diethylphosphono-L-azatyrosine, a Reagent Potentially Useful for the Synthesis of Signal Transduction Related Peptides.,
Synlett, 459-460, 1996. Li Chen, Li Wu, Akira Otaka, Mark S Smyth, Peter P Roller, Terrence R Burke, Den Jen Hertog and Zhong-Yin Zhang :
Why Is Phosphonodifluoromethyl Phenylalanine a More Potent Inhibitory Moiety Than Phosphonomethyl Phenylalanine Toward Protein-Tyrosine Phosphatases,
Biochemical and Biophysical Research Communications, Vol.216, No.3, 976-984, 1995. Motoyoshi Nomizu, W H. Kim, Keizo Yamamura, Atsushi Utani, Sang-Yong Song, Akira Otaka, Peter P. Roller, Hynda K. Kleinman and Yoshihiko Yamada :
Identification of Cell Binding Sites in the Laminin a1 Chain Carboxyl-terminal Globular Domain by Systematic Screening of Synthetic Peptides.,
The Journal of Biological Chemistry, Vol.270, No.35, 20583-20590, 1995.

(要約): The laminin alpha 1 chain carboxyl-terminal globular domain has been identified as a site of multiple biological activities. Using a systematic screening for cell binding sites with 113 overlapping synthetic peptide beads that covered this domain, we found 19 potential active sequences. Corresponding synthetic peptides were evaluated for direct cell attachment, spreading, and inhibition of cell spreading to a laminin-1 substrate using several cell lines. Five peptides (AG-10, AG-22, AG-32, AG-56, and AG-73) showed cell attachment activities with cell-type specificities. Cell spreading on AG-10 was inhibited by beta 1 and alpha 6 integrin antibodies and on AG-32 was inhibited by beta 1, alpha 2, and alpha 6 integrin antibodies. In contrast, cell adhesion and spreading on peptide AG-73 were not inhibited by these antibodies. The minimum active sequences of AG-10, AG-32, and AG-73 were determined to be SIYITRF, IAFQRN, and LQVQLSIR, respectively. These sequences are highly conserved among the different species and different laminin alpha chains, suggesting that they play a critical role for biological function and for interaction with cell surface receptors.
(キーワード): Amino Acid Sequence / Animals / Binding Sites / Cell Adhesion / Cell Line / Dose-Response Relationship, Drug / Fibrosarcoma / Humans / Laminin / Macromolecular Substances / Mice / Molecular Sequence Data / Oligopeptides / Peptide Fragments / 構造活性相関 (structureactivity relationship) / Tumor Cells, Cultured
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 7657636; ● Summary page in Scopus @ Elsevier: 2-s2.0-0029100640

(PubMed: 7657636, Elsevier: Scopus) Hirokazu Tamamura, Tsutomu Murakami, S Horiuchi, K Sugihara, Akira Otaka, W Takada, Toshiro Ibuka, Michinori Waki, Naoki Yamamoto and Nobutaka Fujii :
Synthesis of Protegrin-related Peptides and their Antibacterial and Anti-Human Immunodeficiency Virus Activity.,
Chemical & Pharmaceutical Bulletin, Vol.43, No.5, 853-858, 1995.

(要約): All disulfide analogs (types I, II and III) of protegrin (PG)-1, an 18-residue antimicrobial peptide having two intramolecular disulfide bonds, were synthesized using regioselective disulfide bond formation. Random air-oxidation of the fully reduced PG-1 formed the type III PG-1. In addition, a type III analog containing an amidated carboxy-terminal residue was also prepared. Each analog showed significant and different antibacterial and anti-human immunodeficiency virus (HIV) activity. Deletion of two disulfide bridges caused a significant decrease in activity.
(キーワード): Amino Acid Sequence / Animals / Anti-Bacterial Agents / Anti-Infective Agents / Antimicrobial Cationic Peptides / Antiviral Agents / Candida albicans / Disulfides / Escherichia coli / HIV / Humans / Microbial Sensitivity Tests / Molecular Sequence Data / Peptides / Proteins / Salmonella / Sequence Homology, Amino Acid / Structure-Activity Relationship
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 7553971; ● Search Scopus @ Elsevier (PMID): 7553971

(PubMed: 7553971) Hirokazu Tamamura, Akira Otaka, J Nakamura, K Okubo, T Koide, K Ikeda, Toshiro Ibuka and Nobutaka Fujii :
Disulfide Bond-forming Reaction using Dimethyl sulfoxide/aqueous HCl System and Its Application to Regioselective Two Disulfide Bond Formation.,
International Journal of Peptide and Protein Research, Vol.45, No.4, 312-319, 1995.

(要約): Disulfide bond formation in S-acetamidomethyl (Acm) cysteine-containing peptides by successive treatments with silver trifluoromethanesulfonate (AgOTf) and dimethyl sulfoxide (DMSO)/aqueous HCl is described. An S-Acm cysteine was found to be quantitatively converted into cysteine by deprotection of the Acm group with AgOTf followed by DMSO/aqueous HCl treatment. Under these reaction conditions, no significant side reactions were observed with oxidation-sensitive amino acids such as Met, Tyr and Trp. Oxytocin and a Trp-containing peptide, urotensin II, were prepared by this method. Furthermore, regioselective two disulfide bond formation was found to be feasible by the combination of air oxidation and the AgOTf-DMSO/HCl system. This strategy has been successfully applied to the syntheses of tachyplesin I and endothelin I, which have two disulfide bonds and a Trp residue in the molecule.
(キーワード): Amino Acid Sequence / Antimicrobial Cationic Peptides / Chromatography, High Pressure Liquid / Cysteine / Cystine / DNA-Binding Proteins / Dimethyl Sulfoxide / Disulfides / Endothelins / Hydrochloric Acid / Mass Spectrometry / Molecular Sequence Data / Oxidation-Reduction / Oxytocin / Peptides / Peptides, Cyclic / Silver Compounds / Urotensins
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 7601603; ● Search Scopus @ Elsevier (PMID): 7601603

(PubMed: 7601603) Akira Otaka, Kengo Miyoshi, Hideki Kubota, Terrence R. Burke-Jr, Peter P. Roller, Hirokazu Tamamura and Nobutaka Fujii :
Synthesis and application of N-Boc-L-2-amino-4-(diethylphosphono)-4,4-difluorobutanoic acid for solid-phase synthesis of nonhydrolyzable phosphoserine peptide analogues,
Tetrahedron Letters, Vol.36, No.6, 927-930, 1995. Ronald L. Wange, Noah Isakov, Terrence Burke R. Jr., Akira Otaka, Peter P. Roller, Julian D. Watts, Ruedi Aebersold and Lawrence E. Samelson :
F2(Pmp)2-TAM3, a Novel Competitive Inhibitor of the Binding of ZAP-70 to the T Cell Antigen Receptor, Blocks Early T Cell Signaling,
The Journal of Biological Chemistry, Vol.270, No.2, 944-948, 1995.

(要約): Signaling by the T cell antigen receptor (TCR) is mediated by 17-residue tyrosine-based activation motifs (TAM) present in the cytoplasmic tails of the TCR zeta and CD3 chains. TAMs become tyrosine-phosphorylated upon TCR stimulation, creating a high affinity binding site for the tandem SH2 domains of ZAP-70. In permeabilized T cells, the association of TCR and ZAP-70 was inhibited by a protein tyrosine phosphatase (PTPase)-resistant TAM peptide analog, in which difluorophosphonomethyl phenylalanyl (F2Pmp) residues replaced phosphotyrosine. Inhibition of this association prevented TCR-stimulated tyrosine phosphorylation of ZAP-70 and reduced ZAP-70 kinase activity to basal levels. The reduction in ZAP-70 activity coincided with reduced tyrosine phosphorylation of a number of substrates. Such PTPase-resistant peptides, capable of disrupting SH2 domain-mediated protein-protein interactions, should prove useful in further dissection of multiple signaling pathways and may serve as models for rationally designed chemotherapeutic agents for the treatment of autoimmune and neoplastic disorders.
(キーワード): Amino Acid Sequence / Cells, Cultured / Humans / Molecular Sequence Data / Peptides / リン酸化 (phosphorylation) / Protein Binding / Protein-Tyrosine Kinases / Receptors, Antigen, T-Cell / シグナル伝達 (signal transduction) / Tリンパ球 (T lymphocytes) / Tyrosine / ZAP-70 Protein-Tyrosine Kinase
(出版サイトへのリンク): ● Publication site (DOI): 10.1074/jbc.270.2.944
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 7822334; ● Summary page in Scopus @ Elsevier: 2-s2.0-0028985602

(DOI: 10.1074/jbc.270.2.944, PubMed: 7822334, Elsevier: Scopus) Hirokazu Tamamura, Akira Otaka, W Takada, Y Terakawa, H Yoshizawa, Masao Masuda, Toshiro Ibuka, Tsutomu Murakami, Hideki Nakashima, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Solution-phase synthesis of an anti-human immunodeficiency virus peptide, T22 ([Tyr5,12,Lys7]-polyphemusin II), and the modification of Trp by the p-methoxybenzyl group of Cys during trimethylsilyl trifluoromethanesulfonate deprotection.,
Chemical & Pharmaceutical Bulletin, Vol.43, No.1, 12-18, 1995. Akira Otaka, Kengo Miyoshi, Peter P. Roller, Terrence R. Burke-Jr, Hirokazu Tamamura and Nobutaka Fujii :
Practical Synthesis of Phosphopeptides Using Dimethyl-protected Phosphoamino Acid Derivatives.,
Journal of the Chemical Society. Chemical Communications, Vol.3, 387-389, 1995. Toshiro Ibuka, Kazuo Nakai, Hiromu Habashita, Yuka Hotta, Akira Otaka, Hirokazu Tamamura, Nobutaka Fujii, Norio Mimura, Yoshihisa Miwa, Tooru Taga, Yukiyasu Chounan and Yoshinori Yamamoto :
Aza-Payne Rearrangement of Activated 2-Aziridinemethanols and 2,3-Epoxy Amines under Basic Conditions.,
The Journal of Organic Chemistry, Vol.60, No.7, 2044-2058, 1995. Nobutaka Fujii, Kazuo Nakai, Hirokazu Tamamura, Akira Otaka, Norio Mimura, Yoshihisa Miwa, Tooru Taga, Yoshinori Yamamoto and Toshiro Ibuka :
SN2' Ring opening of aziridines bearing an α,β-unsaturated ester group with organocopper reagents. A new stereoselective synthetic route to (E)-alkene dipeptide isosteres.,
Journal of the Chemical Society, Perkin Transactions 1, 1359-1371, 1995. Kazuo Nakai, Toshiro Ibuka, Akira Otaka, Hirokazu Tamamura, Nobutaka Fujii and Yoshinori Yamamoto :
A One-pot Aza-Payne Rearrangement-Epoxide Ring Opening Reaction of 2-Aziridinemethanols: A Regio- and Stereoselective Synthetic Route to Diastereomerically Pure 1,2-Amino Alocohols.,
Tetrahedron Letters, Vol.36, 6247-6250, 1995. Akira Otaka, Kengo Miyoshi, Midori Kaneko, Hirokazu Tamamura, Nobutaka Fujii, Motoyoshi Nomizu, Terrence R. Burke and Peter P. Roller :
Development of Efficient Two-Step Deprotection Methodology for Dimethyl-Protected Phosphoamino Acid-Containing Peptide Resins and Its Application to the Practical Synthesis of Phosphopeptides,
The Journal of Organic Chemistry, Vol.60, 3967-3974, 1995.

MISC

Kohta Hidaka, JUNYA Hayashi, Daishiro Kobayashi, Masaya Denda and Akira Otaka :
Advanced Insulin Synthesis by One-pot/stepwise Disulfide Bond Formation Enabled by Acid-activated S-Protected Cysteine Sulfoxide in the Presence of Chloride Anion,
ChemRxiv, 2024.

(出版サイトへのリンク): ● Publication site (DOI): 10.26434/chemrxiv-2024-jg5z3
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.26434/chemrxiv-2024-jg5z3

(DOI: 10.26434/chemrxiv-2024-jg5z3) Daishiroh Kobayashi, Masaya Denda, JUNYA Hayashi, Kohta Hidaka, Yutaka Kohmura, Takaaki Tsunematsu, Kohei Nishino, Harunori Yoshikawa, OHKAWACHI Kento, Kiyomi Nigorikawa, Tetsuro Yoshimaru, Naozumi Ishimaru, Nomura Wataru, Toyomasa Katagiri, Hidetaka Kosako and Akira Otaka :
Sulfoxide-mediated Cys-Trp-selective bioconjugation that enables protein labeling and peptide heterodimerization,
ChemRxiv, 2024.

(出版サイトへのリンク): ● Publication site (DOI): 10.26434/chemrxiv-2024-tkv7w-v2
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.26434/chemrxiv-2024-tkv7w-v2

(DOI: 10.26434/chemrxiv-2024-tkv7w-v2) Kaito Anzaki, OHKAWACHI Kento, Daishiroh Kobayashi, Kyan Ryuji, Masaya Denda, Akira Shigenaga and Akira Otaka :
Residue-Specific Modification Reaction Using S-Acetamidomethyl Cysteine Sulfoxide, Cys(Acm)(O),
Peptide Science 2021, 55-56, 2022. Daishiroh Kobayashi, Yutaka Kohmura, Junya Hayashi, Masaya Denda and Akira Otaka :
Development of copper and iron-mediated Cys-Trp-linking reaction,
Peptide Science 2021, 9-12, 2022. OHKAWACHI Kento, Daishiroh Kobayashi, Kyohei Morimoto, Akira Shigenaga, Masaya Denda, Kenzo Yamatsugu, Motomu Kanai and Akira Otaka :
A New Thiol Additive for One-pot Sequential Peptide Ligation-Desulfurization Chemistry,
Peptide Science 2020, 25-26, 2021. Daishiroh Kobayashi, Naoto Naruse, Masaya Denda, Akira Shigenaga and Akira Otaka :
Deprotection of S-Acetamidomethyl Cysteine Mediated by Copper Salts,
Peptide Science 2020, 49-52, 2021. Daishiroh Kobayashi, Kohdai Nishida, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Lossen rearrangement-mediated preparation of N-glyoxylyl peptide without addition of oxidant,
Peptide Science 2019, 59, 2020. Chiaki Komiya, Jun Tsukimoto, Masahiro Ueda, Takuya Morisaki, Tsubasa Inokuma, Akira Shigenaga, Kouji Itou and Akira Otaka :
Preparation of protein thioesters enabled by carboxypeptidase-mediated C-terminal specific hydrazinolysis,
Peptide Science 2018, 8, 2019. Taiki Kohiki, Yusuke Kato, Masaya Denda, Yusuke Nishikawa, Kazuko YORITA, Ikuko Sagawa, Tsubasa Inokuma, Akira Shigenaga, Kiyoshi Fukui and Akira Otaka :
Development and application of novel protein labeling reagent "SEAL",
Peptide Science 2018, 104, 2019. Keitaroh Anyohji, Keisuke Aihara, Tetsuro Yoshimaru, Akira Shigenaga, Toyomasa Katagiri and Akira Otaka :
Development of anti-cancer peptide based on prohibitin 2,
Peptide Science 2018, 46, 2019. Kento Ohkawachi, Kyohei Morimoto, Naoto Naruse, Kenzo Yamatsugu, Akira Shigenaga, Motomu Kanai and Akira Otaka :
Development of methodology for cyclic peptide synthesis using a thiol-incorporated DMAP catalyst,
Peptide Science 2018, 81, 2019. Naoto Naruse, Kiyoka Matsumoto, Akira Shigenaga and Akira Otaka :
Development of method for deprotection of N-terminal thiazolidine derivative using copper salt for chemical protein synthesis,
Peptide Science 2018, 80, 2019. Naoto Naruse, Kento Ohkawachi, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
N-S-acyl-transfer-mediated On-resin Formation of Thioester with Practical Application to Peptide Synthesis,
Peptide Science 2017, 32-33, 2018. Ryo Nadai, Yuki Haraya, Kazuchika Nishitsuji, Kenji Uchimura, Kumiko Sakai-Kato, Akira Shigenaga, Toru Kawakami, Akira Otaka, Hironobu Hojo, Naomi Sakashita and Hiroyuki Saito :
Sulfated glycosaminoglycans promote cell membrane penetration of arginine peptides via enthalpy-driven interactions,
Peptide Science 2016, 141-142, 2017. Shiho Mikawa, Chiharu Mizuguchi, Izumi Morita, Hiroyuki Oyama, Teruhiko Baba, Akira Shigenaga, Toshinori Shimanouchi, Norihiro Kobayashi, Akira Otaka, Kenichi Akaji and Hiroyuki Saito :
Effect of heparin on amyloid fibril formation of apoA-I fragment peptides,
Peptide Science 2016, 149-151, 2017. Yukihiro Itoh, Keisuke Aihara, Paolo Mellini, Toshifumi Tojo, Yosuke Ota, Hiroki Tsumoto, Viswas Raja Solomon, Peng Zhan, Miki Suzuki, Daisuke Ogasawara, Akira Shigenaga, Tsubasa Inokuma, Hidehiko Nakagawa, Naoki Miyata, Tamio Mizukami, Akira Otaka and Takayoshi Suzuki :
Design, synthesis and biological evaluation of SNAIL1 peptide-based lysine specific demethylase 1 inhibitors,
Peptide Science 2016, 165-166, 2017. Kohsuke Yamaoka, Keisuke Aihara, Naoto Naruse, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
One-pot sequential native chemical ligations using photocaged crypto-thioester,
Peptide Science 2016, 73-74, 2017. Takuya Morisaki, Masaya Denda, Jun Yamamoto, Daisuke Tsuji, Tsubasa Inokuma, Kouji Itou, Akira Shigenaga and Akira Otaka :
Development of N-sulfanyltehylanilide (SEAlide)-based traceable linker for enrichment and selective labeling of target proteins,
Peptide Science 2016, 179-181, 2017. Takahiro Nakamura, Akira Shigenaga, Naoto Naruse, Tsubasa Inokuma and Akira Otaka :
Tailored Synthesis of 162-Residue S-Monoglycosylated GM2-Activator Protein (GM2AP) Analogues Applicable to the Preparation of a Protein Library,
Peptide Science 2016, 75-76, 2017. Chiaki Komiya, Keisuke Aihara, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Intein-inspired amide bond processing device,
EPS Proceedings 2016, 60, 2016. Takahiro Nakamura, Akira Shigenaga, Naoto Naruse, Tsubasa Inokuma, Kouji Itou and Akira Otaka :
Second-generation synthetic strategy of GM2-activator protein (GM2AP) analogues applicable to the preparation of a protein library,
EPS Proceedings 2016, 63, 2016. Keisuke Aihara, Kohsuke Yamaoka, Naoto Naruse, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
One-pot/sequential native chemical ligation using photo-responsive crypto-thioester,
EPS Proceedings 2016, 39, 2016. Rin Miyajima, Yusuke Tsuda, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Preparation of peptide thioesters from naturally occuring sequences using a chemical protocol,
Peptide Science 2015, 21-22, 2016. Chiaki Komiya, Keisuke Aihara, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Development of intein-inspired peptide bond processing device,
Peptide Science 2015, 281-282, 2016. Kohei Tsuji, Kohei Sato, Mitsuhiro Eto, Yusuke Tsuda, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
N-Sulfanylethylanilide (SEAlide) peptide as a versatile intermediate for protein chemical synthesis using native chemical ligation,
Peptide Science 2014, 113-116, 2015. Jun Yamamoto, Miku Kita, Akira Shigenaga, Youichi Sato, Aiko Yamauchi and Akira Otaka :
Development of thiol-responsive traceable linker for efficient enrichment and selective labeling of target proteins,
Peptide Science 2013, 205-206, 2014. Keisuke Aihara, Akira Shigenaga, Daisuke Takahashi and Akira Otaka :
New approach for synthesis of lactam bridged peptides using olefin metathesis on AJIPHASE®,
Peptide Science 2013, 143-144, 2014. Miku Kita, Jun Yamamoto, Koji Ebisuno, Chiaki Komiya, Akira Shigenaga, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Akira Otaka :
Development of hydrogen peroxide-responsive amide bond cleavage device,
Peptide Science 2013, 203-204, 2014. Yusuke Tsuda, Akira Shigenaga, Kohei Sato, Takahiro Nakamura and Akira Otaka :
Development of chemical protocols for producing peptide thioesters from naturally occurring peptide sequences,
Peptide Science 2013, 157-158, 2014. Takahiro Nakamura, Akira Shigenaga, Kohei Sato, Yusuke Tsuda, Ken Sakamoto and Akira Otaka :
Application of peptidyl prolyl thioesters to native chemical ligation,
Peptide Science 2013, 93-94, 2014. Ken Sakamoto, Kohei Sato, Akira Shigenaga, Daisuke Tsuji, Kouji Itou and Akira Otaka :
N-Sulfanylethyl anilide linkers as peptide thioester equivalent,
Peptides Across The Pacific, Proceedings of the Twenty-Third American and Sixth International Peptide Symposium, 242-243, 2013. Akira Shigenaga, Keiji Ogura, Hiroko Hirakawa, Jun Yamamoto, Koji Ebisuno, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Akira Otaka :
Design and synthesis of hypoxia-responsive amino acid which causes peptide bond cleavage in hypoxic cells,
Peptide Science 2012, 135-136, 2013.

(キーワード): hypoxia-responsive / peptide bond cleavage / prodrug / stimulus-responsive / trimethyl lock
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1570854176180146304

(CiNii: 1570854176180146304) Kohei Sato, Keisuke Kitakaze, Ken Sakamoto, Akira Shigenaga, Daisuke Tsuji, Kouji Itou and Akira Otaka :
Convergent chemical synthesis of human GM2 activator protein analog using SEAlide chemistry,
Peptide Science 2012, Vol.2012, 13-14, 2013.

(キーワード): GM2 activator protein / protein chemical synthesis / SEAlide peptide
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1571135651156844416

(CiNii: 1571135651156844416) Kohei Tsuji, Kosuke Tanegashima, Akira Shigenaga, Keisuke Aihara, Masaya Denda, Hao Ding, Takahiko Hara and Akira Otaka :
Synthesis of antagonistic peptide for putative CXCL14 receptor protein and their identification,
Peptide Science 2012, Vol.2012, 31-32, 2013.

(キーワード): chemokine / receptor / dimer / -helix / antagonist
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1571980076086973440

(CiNii: 1571980076086973440) Ken Sakamoto, Kohei Sato, Akira Shigenaga, Kohei Tsuji, Shugo Tsuda, Hajime Hibino, Yuji Nishiuchi and Akira Otaka :
Development of efficient synthetic protocol for Fmoc amino acid-incorporated N-sulfanylethyl-aniline linker as peptide thioester precursor,
Peptide Scinece 2012, Vol.2012, 165-166, 2013.

(キーワード): native chemical ligation / N-S acyl transfer / peptide thioester / SEAlide peptide
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1572261551063693056

(CiNii: 1572261551063693056) Akira Shigenaga, Hiroko Hirakawa, Jun Yamamoto, Keiji Ogura, Masaya Denda, Keiko Yamaguchi and Akira Otaka :
Caged ceramide which releases parent ceramide after UV-induced amide bond cleavage followed by intramolecular O-N acyl transfer,
Peptide Science 2011, 385-386, 2012.

(キーワード): caged compound / ceramide / sphingolipid / trimethyl lock / UV
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1570572700793231232

(CiNii: 1570572700793231232) Hao Ding, Kohei Sato, Ko Morishita, Akira Shigenaga and Akira Otaka :
Doubly-kinetically controlled proline ligation,
Peptide Science 2011, 133-134, 2012.

(キーワード): kinetically controlled ligation / native chemical ligation / peptide synthesis / proline / SEAlide peptide
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1570854175769778944

(CiNii: 1570854175769778944) Kohei Sato, Shugo Tsuda, Ken Sakamoto, Akira Shigenaga and Akira Otaka :
N-Sulfanylethylanilide peptide: a peptide thioester equivalent which can directly participate in native chemical ligation,
Peptide Science 2011, 13-14, 2012.

(キーワード): kinetically controlled NCL / native chemical ligation / N-S acyl transfer / peptide thioester / SEAlide peptide
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1570009750839756800

(CiNii: 1570009750839756800) Kohei Sato, Shugo Tsuda, Kohei Tsuji, Ken Sakamoto, Akira Shigenaga and Akira Otaka :
N-Sulfanylethylanilide derivative as a peptide thioester equivalent,
Proceedings of the Twenty-Second American Peptide Symposium, 72-73, 2011. Kohei Tsuji, Yoshitake Sumikawa, Kosuke Tanegashima, Akira Shigenaga, Takahiko Hara and Akira Otaka :
Synthesis of CXCL14 and its derivatives utilizing C to N or N to C directive sequential NCL protocol,
Proceedings of the Twenty-Second American Peptide Symposium, 74-75, 2011. Akira Otaka and Akira Shigenaga :
Development of amide bond cleavage device with application to chemical biology use,
Peptide Science 2010, Vol.2010, No.0, 49, 2011.

(キーワード): amide bond cleavage / chemical biology / peptide bond cleavage / stimulus-responsive / UV-responsive
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1572261550741345024

(CiNii: 1572261550741345024) Kohei Tsuji, Yoshitake Sumikawa, Kosuke Tanegashima, Akira Shigenaga, Takahiko Hara and Akira Otaka :
Synthesis and biological evaluation of CXCL14 and its derivatives,
Peptide Science 2010, Vol.2010, No.0, 182, 2011.

(キーワード): biological activity / chemokine / native chemical / ligation / protein synthesis / thioacid
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1573105975671357056

(CiNii: 1573105975671357056) Akira Shigenaga, Jun Yamamoto, Naomi Nishioka, Masaya Denda and Akira Otaka :
Enantioselective synthesis of stimulus-responsive amino acid via pyrrolidinyl tetrazole catalyzed asymmetric -amination of aldehyde,
Peptide Science 2010, Vol.2010, No.0, 202, 2011.

(キーワード): asymmetric -amination / organocatalyst / peptide bond cleavage / stimulus-responsive / UV-responsive
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1572824500694759936

(CiNii: 1572824500694759936) Kohei Sato, Shugo Tsuda, Nami Maeda, Masaya Denda, Akira Shigenaga and Akira Otaka :
Native chemical ligation using N-peptidyl anilide as crypto-thioester,
Peptide Science 2010, Vol.2010, No.0, 203, 2011.

(キーワード): Fmoc SPPS / native chemical ligation / N-S acyl transfer / peptide thioester / protein synthesis
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1573950400601602304

(CiNii: 1573950400601602304) Keiji Ogura, Hiroko Hirakawa, Akira Shigenaga and Akira Otaka :
Synthesis of nonhydrolyzable AMPylated amino acid analogues for uncovering the physiological role of AMPylation,
Peptide Science 2010, Vol.2010, No.0, 205, 2011.

(キーワード): AMPylation / cellular signaling / mimetics / nonhydrolyzable / protein modification
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1570854175857789184

(CiNii: 1570854175857789184) Jun Yamamoto, Nami Maeda, Masaya Denda, Akira Shigenaga and Akira Otaka :
Development of recapturable cleavable linker for efficient enrichment and specific labeling of target proteins,
Peptide Science 2010, Vol.2010, No.0, 232, 2011.

(キーワード): cleavable linker / peptide bond cleavage / target identification / selective labeling / stimulus-responsive
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1573668925624452736

(CiNii: 1573668925624452736) Ko Morishita, Keiko Yamaguchi, Hao Ding, Akira Shigenaga, Kenichi Akaji and Akira Otaka :
Development of stimulus responsive thiol releasing system for controlling activity of cysteine protease,
Peptide Science 2010, Vol.2010, No.0, 290, 2011.

(キーワード): activity control / cysteine protease / Michael addition / S-alkylation / UV-responsive
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1573950400601248256

(CiNii: 1573950400601248256) Akira Shigenaga, Yukiko Nishiyama, Nami Maeda and Akira Otaka :
Synthesis of cyclic peptides via on resin-intramolecular native chemical ligation followed by reductive release from resin,
Peptide Science 2009, 147-148, 2010. Akira Shigenaga, Naomi Nishioka, Jun Yamamoto, Hiroko Hirakawa, Yoshitake Sumikawa, Keiko Yamaguchi and Akira Otaka :
Influence of an amino acid sequence on kinetics of peptide bond cleavage reaction induced by a stimulus-responsive amino acid,
Peptide Science 2008, 395-396, 2009. Yoshitake Sumikawa, Shugo Tsuda, Akira Shigenaga and Akira Otaka :
The application of peptide thioacids to NCL-type sequential condensation of peptide fragments,
Peptide Science 2008, 175-176, 2009. Yoko Yamaki, Akira Shigenaga and Akira Otaka :
Synthesis of fluoroalkene dipeptide isostere utilizing intramolecular redox reaction,
Peptide Science 2008, 49-50, 2009. Shugo Tsuda, Nami Maeda, Kiyomi Bando, Akira Shigenaga and Akira Otaka :
Synthesis of peptide thioester using N-substituted aniline derivatives,
Peptide Science 2008, 17-18, 2009. Akira Shigenaga, Daisuke Tsuji, Naomi Nishioka, Shugo Tsuda, Kouji Itou and Akira Otaka :
Development of stimulus-responsive amino acid with peptide bond-cleavage ability and its application to a nucleocytoplasmic shuttle peptide,
Peptide Science 2007, Vol.2007, 97-98, 2008.

(キーワード): nuclear export signal (NES) / nuclear localization signal (NLS) / stimulus responsive / trimethyl lock / UV irradiation
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1573950400368902528

(CiNii: 1573950400368902528) Yoshikazu Sasaki, Takashi Tsuji, Ayumu Niida, Akira Shigenaga, Nobutaka Fujii and Akira Otaka :
Regio- and stereoselective synthesis of (Z)-alkene cis-Xaa-Pro dipeptide mimetics,
Peptides 2006, 126-127, 2007. Takashi Tsuji, Yoshikazu Sasaki, Keiko Yamaguchi, Akira Shigenaga, Nobutaka Fujii and Akira Otaka :
Synthesis of (Z)-alkene cis-Xaa-Pro type dipeptide isosteres using organocopper-mediated anti-SN2' reactions,
Peptide Science 2006, 327, 2006. Akira Shigenaga, Saori Shintaku and Akira Otaka :
Development of photo-responsive self-processing peptides,
Peptide Science 2006, 92, 2006. Satoshi Ueda, Akira Otaka, Hirokazu Tamamura and Nobutaka Fujii :
4-(Dimethylamino)phenacyl Group: New Photoremovable Protecting Group for Amines and Carboxylic Acids,
Peptide Science 2004, Vol.2004, 599-602, 2005.

(キーワード): photoremovable protecting group / phenacyl group / native chemical ligation
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1570854174923822592

(CiNii: 1570854174923822592) Terukazu Kato, Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Synthesis of β-Secretase Inhibitors Containing a Hydroxyethylamine Dipeptide Isostere and their Structure-activity Relationship Studies,
Peptide Science 2004, Vol.2004, 515-516, 2005.

(キーワード): β-secretase inhibitor / hydroxyethylamine / isostere / HDI / Aβ
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1570854174923778176

(CiNii: 1570854174923778176) Hirokazu Tamamura, Takanobu Araki, Ai Esaka, Satoshi Ueda, Shinya Oishi, Zixuan Wang, Stephen C. Peiper, Akira Otaka and Nobutaka Fujii :
Development of Low Molecular Weight CXCR4 Antagonists by Exploratory Structural Tuning of Cyclic Tetrapeptide-scaffolds,
Peptide Science 2004, Vol.2004, 509-510, 2005.

(キーワード): chemokine receptor / CXCR4 / cyclic peptides / FC131 / T140
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1572824499760752512

(CiNii: 1572824499760752512) Hirokazu Tamamura, Kenichi Hiramatsu, Satoshi Ueda, Takanobu Araki, M Takenaga, R Igarashi, Akira Hori, Naoyuki Kanzaki, Miho Fujisawa, Hideki Nakashima, Naoki Yamamoto, Akira Otaka and Nobutaka Fujii :
The Chemokine Receptor CXCR4 as a Therapeutic Target for Several Diseases Including AIDS, Cancer and Rheumatoid Arthritis,
Peptide Science 2004, Vol.2004, 121-122, 2005.

(キーワード): cancer metastasis / chemokine receptor / CXCR4 / HIV second receptor / rheumatoid arthritis
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1573105974741577856

(CiNii: 1573105974741577856) Ayumu Niida, Makiko Mizumoto, Yoshikazu Sasaki, Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Stereoselective Synthesis of Diketopiperazine Mimmetics as Promising Scaffolds for Drug Discovery Utilizing Organocopper-Mediated anti-S_N2' Reaction,
Peptide Science 2004, 169-172, 2005. S Mizokami, Hirokazu Tamamura, Kenichi Hiramatsu, Makiko Mizumoto, Miki Akamatsu, Hideki Nakashima, Zixuan Wang, Stephen C. Peiper, Naoki Yamamoto, Akira Otaka and Nobutaka Fujii :
New Leads of Low Molecular Weight CXCR4 Antagonists Based on Enhancement of the T140-based Pharmacophores,
Peptide Science 2003, Vol.2003, No.0, 285-288, 2004.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1574231874864552704

(CiNii: 1574231874864552704) Terukazu Kato, Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Development of Potent β-Secretase Inhibitors Containing a Hydroxyethylamine Dipeptide Isostere,
Peptide Science 2003, Vol.2003, No.0, 231-234, 2004.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1572824499981164288

(CiNii: 1572824499981164288) Hirokasu Tamamura, Akira Hori, Naoyuki Kanzaki, Kenichi Hiramatsu, Makiko Mizumoto, Hideki Nakashima, Naoki Yamamoto, Akira Otaka and Nobutaka Fujii :
CXCR4 Antagonists Identified as Anti-Cancer Metastatic Agents,
Peptide Science 2003, Vol.2003, No.0, 65-68, 2004.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1573950399887592448

(CiNii: 1573950399887592448) Takanobu Araki, Satoshi Ueda, Kenichi Hiramatsu, Shinya Oishi, Hirokazu Tamamura, Akira Otaka, Nobutaka Fujii, Shuichi Kusano, Shigemi Terakubo, Hideki Nakashima, Zixuan Wang and Stephen C. Peiper :
A New Strategy for Molecular-size Reduction Bioactive Peptide, Using Two Orthogonal Libraries of Cyclic Peptided,
Peptide Science 2003, 207-210, 2004. Satoshi Ueda, Kenji Tomita, Akira Otaka, Hirokazu Tamamura, Yoshiaki Yano, Katsumi Matsuzaki and Nobutaka Fujii :
Synthesic Studies on 7TM-GPCR (I):Lipid Bilayer Assisted Membrane Peptide Ligation,
Peptide Science 2003, Vol.40, 53-56, 2004. Akira Otaka, Yoshikazu Sasaki, Fumihiko Katagiri, Shinya Oishi, Hirokazu Tamamura and Nobutaka Fujii :
Synthesis of(E)-Alkene trans-Xaa-Pro Mimetics Using Organocopper Reagents,
Peptide Science 2002, Vol.2002, No.0, 357-360, 2003.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1570009751822974592

(CiNii: 1570009751822974592) Kenichi Hiramatsu, Hirokazu Tamamura, Hideki Nakashima, Akira Otaka and Nobutaka Fujii :
Synthesis of CXCR4 Antagonists,T140 Derivatives with Improved Biostability, and Their SAR Study,
Peptide Science 2002, Vol.2002, No.0, 213-216, 2003.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1573387451543475456

(CiNii: 1573387451543475456) Akira Otaka, Miki Nakamura, Eiichi Kodama, Syota Nakamura, Hiroaki Nakano, Susumu Uchiyama, Hirokazu Tamamura, Masao Matsuoka, Yuji Kobayashi and Nobutaka Fujii :
Development of Fusion-inhibiting Anti-HIV-1 Peptides Based on the Structure of Molecular Complex Involved in HIV-1-cell Fusion,
Peptide Science 2002, Vol.2002, No.0, 65-68, 2003.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1573105976559944192

(CiNii: 1573105976559944192) Hirokazu Tamamura, Terukazu Kato, Tadakazu Hori, Akira Otaka and Nobutaka Fujii :
Stereoselective Synthesis of Peptidomimetics with Hydroxyethylamine Diepetide Isosteres Utilizing Aza-Payne Rearrangement and O,N-Acyl Transfer Reactions,
Peptide Science 2002, 143-146, 2003. K Nemoto, Hirokazu Tamamura, S Mizokami, Shinya Oishi, Akira Otaka and Nobutaka Fujii :
Acid-catalyzed Ring-opening Reactions of β-Aziridinyl-α,β-enoates and Their Application,
Peptide Science 2002, 139-142, 2003. K. Takeshima, A. Chikushi, S Kobayashi, L. Kyung-Kwon, S Yonehara, Akira Otaka, Nobutaka Fujii and K Matsuzaki :
Translocation of Basic Peptides through Human Cell Membranes,
Peptide Science 2001, Vol.2001, No.0, 321-324, 2002.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1572824499551973120

(CiNii: 1572824499551973120) Shinya Oishi, Takae Kamano, Ayumu Niida, Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Synthesis of ψ[(E)-CH=CMe]- and ψ[(Z)-CH=CMe]-type Dipeptide Isosteres and Their Application to a Cyclic RGD Peptide,
Peptide Science 2001, Vol.2001, No.0, 241-244, 2002.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1571980074621882880

(CiNii: 1571980074621882880) Miki Nakamura, Akira Otaka, Eiichi Kodama, Masao Matsuoka, Susumu Uchiyama, Syota Nakamura, Yuji Kobayashi, Hirokazu Tamamura and Nobutaka Fujii :
Design and Synthesis of Highly Active Anti-HIV Peptide Based on gp41-C34 Peptide,
Peptide Science 2001, Vol.2001, No.0, 73-76, 2002.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1573105974528834048

(CiNii: 1573105974528834048) Junko Watanabe, Akira Otaka, Hideaki Watanabe, Akira Yukimasa, Hirokazu Tamamura and Nobutaka Fujii :
Synthesis of Fluoroalkene Dipeptide Isosteres Utilizing Organocopper or SmI₂ Reagents,
Peptide Science 2001, Vol.2001, No.0, 29-32, 2002.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1574231874435524736

(CiNii: 1574231874435524736) Ayumu Niida, Shinya Oishi, Takae Kamano, Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Synthesis of ψ[(E)-CMe=CMe]- and ψ[(E)-CMe=CH]-type Alkene Dipeptide Isosteres from a Chiral Amino Acide,
Peptide Science 2001, 237-240, 2002. Kenichi Hiramatsu, Hirokazu Tamamura, Akane Omagari, Hideki Nakashima, Younong Xu, Masao Matsuoka, Akira Otaka and Nobutaka Fujii :
Synthesis of Novel Anti-HIV Peptides Based on a CXCR4 Antagonist, T140, and Their SAR Study,
Peptide Science 2001, 175-178, 2002. Akira Otaka, Miki Nakamura, Eiichi Kodama, Susumu Uchiyama, Hirokazu Tamamura, Yuji Kobayashi, Masao Matsuoka and Nobutaka Fujii :
Artificial Remodeling of gp41-C34 Peptide Leads to Effective HIV Fusion Inhibitor with High anti-HIV Activity,
Peptide 2002, 838-839, 2002. Shinya Oishi, Takae Kamano, Ayumu Niida, Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Organocopper-mediated Stereoselective Synthesis of multi-Substituted Alkene Dipeptide Isosteres and Application to cyclic RGD Peptides,
Peptide 2002, 244-245, 2002. Shinya Oishi, Takae Kamano, Ayumu Niida, M. Kwaguchi, Ryo Hosotani, Masayuki Imamura, N. Yawata, Keiichi Ajito, Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Efficient Synthesis of Cyclic RGD Pseudopeptide with (E)-Alkene Dipeptide Isosteres and Its Biological Activity,
Peptide Science 2000, 249-250, 2001. Akane Omagari, Hirokazu Tamamura, Shinya Oishi, Hideki Nakashima, Akira Otaka and Nobutaka Fujii :
Development of Specific CXCR4 Inhibitors Based on an anti-HIV peptide, T140, and Their Structure-Activity Relationship Study,
Peptide Science 2000, 129-132, 2001. Akira Otaka, Etsuko Mitsuyama, Hideaki Watanabe, Hirokazu Tamamura, T Hayashi, K. Nakao and Nobutaka Fujii :
Stereoselective Synthesis of CF₂ or CHF-Substituted Phosphoamino Acids and Their Incorporation into Peptide,
Peptide Science 2000, 17-20, 2001. Akira Otaka, Hideaki Watanabe, Junko Watanabe, Hirokazu Tamamura and Nobutaka Fujii :
Synthesis of Fluoroalkene Dipeptide Isosteres Utilizing Organometallic Reagents,
Peptides: The Wave of the Future, 606-607, 2001. Akira Otaka, Y. Umeda, Shinya Oishi, Toshiro Ibuka and Nobutaka Fujii :
New Strategy for the Synthesis of Aspartyl Protease Inhibitor Based on "Aza-Payne Rearrangement",
Peptide Science 1999, 195-196, 2000. Nobutaka Fujii, M Hirohashi, Shinya Oishi, M Akaji, Akane Omagari, Akira Otaka and Toshiro Ibuka :
Application of Ring Closing Olefin Metathesis to the Conformational Restriction of Biological Active Peptide,
Peptide Science 1999, 193-194, 2000. Motoyoshi Nomizu, Yuichiro Kuratomi, Akira Otaka, Hynda K. Kleinman, Yoshihiko Yamada and Norio Nishi :
Identification of Biologically Active Peptides in Laminin-1,
Peptide Science 1999, 21-24, 2000. M Hirohashi, Shinya Oishi, Tsutomu Murakami, Rieko Arakaki, Younong Xu, Toshio Hattori, Naoki Yamamoto, Takatomo Koshiba, Ryo Hosotani, Masayuki Imamura, T Mio, S Nagai, T Izumi, Hirokazu Tamamura, Akira Otaka and Nobutaka Fujii :
Synthesis of a CC Chemokine vMIP-II,Encoded by Kaposi's Sarcoma-associated Herpesvirus and Its Biological Activity,
Peptide Science 1998, 285-288, 1999. Akira Otaka, Etsuko Mitsuyama, Kengo Miyoshi and Nobutaka Fujii :
Synthesis of Nonhydrolyzable Phosphthreonine Derivatives and Their Practical Application to Peptide Synthesis,
Peptide Science 1998, 137-140, 1999. Hirokazu Tamamura, Akane Omagari, Tsutomu Murakami, Rieko Arakaki, Younong Xu, Toshio Hattori, Michinori Waki, Akiyoshi Matsumoto, Hideki Nakashima, Naoki Yamamoto, Akira Otaka and Nobutaka Fujii :
HIV-cell Fusion Inhibitors:T22 and Its Downsized Analogs with High Activity,
Peptide Science 1998, 49-52, 1999. Kengo Miyoshi, Akira Otaka, Midori Kaneko, Hirokazu Tamamura and Nobutaka Fujii :
Convenient Preparation of Phosphopeptide Fagments Using High TFMSA System and Its Application to Synthesis of Long Chain Phosphopeptides,
Peptide Science Present and Future, 507-509, 1999. Akira Otaka, Y. Umeda, Hirokazu Tamamura, Toshiro Ibuka and Nobutaka Fujii :
Synthesis of Protected 2,3-Epoxy Amines Utilizing Aza-Payne Rearrangement of Activated 2-Aziridinemethanols Under Basic Conditions,
Peptide Science Present and Future, 504-506, 1999. Hirokazu Tamamura, Michinori Waki, Akira Otaka, Tsutomu Murakami, Hideki Nakashima, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Efficient Analog of An Anti-HIV Peptide,T22 ([Tyr5,12,Lys7]-polyphemusin II),Having Low Cytotoxicity,
Peptide Science Present and Future, 427-429, 1999. Hirokazu Tamamura, Michinori Waki, Akira Otaka, Tsutomu Murakami, Hideki Nakashima, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
HIV-cell Fusin Inhibitor T22([Tyr5,12,Lys7]-polyphemusin II),and Its Related Compounds,
Peptide Science Present and Future, 424-426, 1999. Hirokazu Tamamura, F Matsumoto, Kyoko Sakano, Akira Otaka, Tsutomu Murakami, Hideki Nakashima, Michinori Waki, Akiyoshi Matsumoro, Naoki Yamamoto and Nobutaka Fujii :
An Anti-HIV Peptide T22 is Confirmed to Be a Selective CXCR4/Fusin Inhibitor by Comparative Inhibition Study of a Chemokine SDF-1,Synthesized by Regioselective Disulfide Bond Formation,
Peptide Science Present and Future, 398-402, 1999. Hirokazu Tamamura, Masaki Yamashita, Hiroyuki Muramatsu, Toshiro Ibuka, Akira Otaka and Nobutaka Fujii :
Stereoselctive Synthesis of Two Type (E)-Alkene Dipeptide Isosteres from a Single Substrate of β-Aziridinyl-α ,β-enoate,
Peptide Science Present and Future, 44-46, 1999. Hirokazu Tamamura, Tsunehito Ishihara, Hiromi Oyake, Akira Otaka and Nobutaka Fujii :
Convenient One-pot Synthesis of Cystine-containing Peptides from Protected Peptidyl Resins and Its Application to the Synthesis of Bifunctional Anti-HIV Compounds,
Peptide Science Present and Future, 41-43, 1999. H. Mariko, Hirokazu Tamamura, Akira Otaka, Toshiro Ibuka, Rieko Arakaki, Hideki Nakashima and Nobutaka Fujii :
Ring-closing Metathesis Produced a CXCR4 Antagonist with Anti-HIV Activity,
Peptide 1998, 662-663, 1999. Akira Otaka, Etsuko Mitsuyama, Shinya Oishi, Kengo Miyoshi, Hirokazu Tamamura and Nobutaka Fujii :
Synthesis of Nonhydrolyzable Phosphothreonine Mimetic and Its Practical Application to Peptide Synthesis,
Peptide 1998, 264-265, 1999. Akira Otaka, Kengo Miyoshi, Midori Kaneko, Terrence Jr R. Burke, Peter P. Roller, Hirokazu Tamamura and Nobutaka Fujii :
Development of New Efficient Deprotecting Methodologies for The Synthesis of Phosphoamino Acids-Containing Peptides,
Peptides 1996, 701-702, 1998. Hirokazu Tamamura, Akira Otaka, Tsutomu Murakami, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Identification of a Polyphemusin Analog (T22)- Zn(II) complex by Mass Spectrometric Analysis and Its Anti-HIV Activity,
Peptide Chemistry 1996, 269-272, 1997. W Takada, Akira Otaka, Kazuo Nakai, Toshiro Ibuka, Koji Fujimoto, M Wada, Ryuichiro Doi, Ryo Hosotani, S Higashide, Masayuki Imamura and Nobutaka Fujii :
Synthesis and Biological Activity of Bombesin Analogues Containing (E)-Alkene Dipeptide Isosteres,
Peptide Chemistry 1995, 493-496, 1996. Hirokazu Tamamura, Akira Otaka, Tsutomu Murakami, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Identification of Binding Proteins of an Anti-HIV Peptide,T22,
Peptide Chemistry 1995, 237-240, 1996. Kengo Miyoshi, Akira Otaka, Midori Kaneko, Hirokazu Tamamura and Nobutaka Fujii :
Practical Phosphopeptides Synthesis Using Dimethylphosphono Amino Acids (No.2),
Peptide Chemistry 1995, 25-28, 1996. Motoyoshi Nomizu, Atsushi Utani, Akira Otaka, Peter P. Roller and Yoshihiko Yamada :
Assembly and Stability of Double- and Triple-stranded α-Helical Coiled-coil Structures of Laminin Peptides,
Peptides: Chemistry, Structure and Biology, 487-488, 1996. Akira Otaka, Kengo Miyoshi, Hirokazu Tamamura, Peter P. Roller, Terrence R. Burke-Jr and Nobutaka Fujii :
Development of a Practical Synthetic Methodology Using Dimethylphosphono Amino Acid for Phosphopeptides,
Peptides: Chemistry, Structure and Biology, 442-443, 1996. Hirokazu Tamamura, K Sugihara, Akira Otaka, Tsutomu Murakami, S Horiuchi, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Synthesis of Protegrin-related Peptides and their Antibacterial and Anti-HIV Activity.,
Peptide Chemistry 1994, 345-348, 1995. Akira Otaka, Kengo Miyoshi, Terrence R. Burke-Jr, Peter P. Roller, Hirokazu Tamamura and Nobutaka Fujii :
Application of Ser(OPO₃Me₂) Derivatives to The Synthesis of Phosphoserine-containing peptide,
Peptide Chemistry 1994, 193-196, 1995. K. Suzuki, Toshiro Ibuka, Tooru Taga, Yoshihisa Miwa, Norio Mimura, Akira Otaka and Nobutaka Fujii :
Stereoselective Synthesis of L-Vinylglycine Derivatives,
Peptide Chemistry 1994, 165-168, 1995. Hirokazu Tamamura, Y Terakawa, Masao Masuda, Akira Otaka, H Murakami, Hideki Nakashima, S Horiuchi, Michinori Waki, Akiyoshi Matsumoto, Naoki Yamamoto and Nobutaka Fujii :
Structure-Activity Relationships of An Anti-HIV Peptide, T-22(No.2),
Peptide Chemistry 1994, 153-156, 1995. Akira Otaka, Kengo Miyoshi, Terrence R. Burke-Jr, Peter P. Roller, Hirokazu Tamamura and Nobutaka Fujii :
Synthesis and Biological Activity of Phosphatases Resistant Phosphoamino Acid Mimetics Containing Peptides,
Peptide Chemistry 1994, 9-12, 1995. Nobutaka Fujii, Kazuo Nakai, Hiromu Habashita, Akira Otaka, Toshiro Ibuka, N Wada, Ryuichiro Doi, Ryo Hosotani, Masayuki Imamura, F Garrido, A Mann, Yukiyasu Chounan and Yoshinori Yamamoto :
Highly Stereoselective Synthesis of (E)-Alkene Dipeptide Isosters via Organocopper Mediated 1,3-Chirality Transfer Reaction and Its Application to The Synthesis of Potent Bombesin Antagonist with No Agonistic Activity,
Peptide 1994, 77-78, 1995.

総説・解説

Masaya Denda and Akira Otaka :
Advances in Preparation of Peptide and Protein Thioesters Aiming to Use in Medicinal Sciences,
Chemical & Pharmaceutical Bulletin, Vol.70, No.5, 316-323, May 2022.

(出版サイトへのリンク): ● Publication site (DOI): 10.1248/cpb.c21-01019
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.1248/cpb.c21-01019

(DOI: 10.1248/cpb.c21-01019) 重永章, 大髙章 :
有機化学的視点からの標的タンパク質精製・機能解明ツールの開発,
生化学, Vol.91, No.6, 795-799, 2019年12月.

(出版サイトへのリンク): ● Publication site (DOI): 10.14952/SEIKAGAKU.2019.910795
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.14952/SEIKAGAKU.2019.910795

(DOI: 10.14952/SEIKAGAKU.2019.910795) 大髙章 :
弁証法的薬学教育観-薬学における有機化学教育を考える-,
有機合成化学協会誌, Vol.76, No.7, 667, 2018年7月.

(出版サイトへのリンク): ● Publication site (DOI): 10.5059/yukigoseikyokaishi.76.667
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.5059/yukigoseikyokaishi.76.667

(DOI: 10.5059/yukigoseikyokaishi.76.667) 大髙章, 重永章 :
十字路:Native Chemical Ligation法,
有機合成化学協会誌, Vol.76, No.1, 66, 2018年1月.

(出版サイトへのリンク): ● Publication site (DOI): 10.5059/yukigoseikyokaishi.76.66
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.5059/yukigoseikyokaishi.76.66

(DOI: 10.5059/yukigoseikyokaishi.76.66) 大髙章, 重永章 :
天然に学ぶタンパク質合成化学,
有機合成化学協会誌, Vol.76, No.1, 45-54, 2018年1月.

(出版サイトへのリンク): ● Publication site (DOI): 10.5059/yukigoseikyokaishi.76.45
(文献検索サイトへのリンク): ● Search Scopus @ Elsevier (DOI): 10.5059/yukigoseikyokaishi.76.45

(DOI: 10.5059/yukigoseikyokaishi.76.45) 鳴海哲夫, 大髙章 :
第3章第3節ペプチドの不安定性を解決するペプチド結合の置換技術,
ペプチド医薬品のスクリーニング・安定化・製剤化技術, 130-140, 2017年12月. Akira Shigenaga, Jun Yamamoto, Taiki Kohiki, Tsubasa Inokuma and Akira Otaka :
Invention of stimulus-responsive peptide-bond-cleaving residue (Spr) and its application to chemical biology tools,
Journal of Peptide Science, Vol.23, 505-513, Aug. 2017.

(要約): Elucidation of biological functions of peptides and proteins is essential for understanding peptide/protein-related biological events and developing drugs. Caged peptides and proteins that release a parent active peptide/protein by photo-irradiation have successfully been employed to elucidate the functions. Whereas the usual caged peptide/protein enables conversion of an inactive form to an active form (OFF-to-ON conversion) by photo-induced deprotection, photo-triggered main chain cleavage is reported to be applicable to ON-to-OFF conversion. These peptides and proteins are photo-responsive; however, if peptides and proteins could respond to other stimuli such as disease-related environment or enzymes, their range of application should be widened. To convert the photo-responsive peptide/protein into other stimulus-responsive peptide/protein, quite laborious de novo design and synthesis of the stimulus-responsive unit are required. In this context, we designed a stimulus-responsive peptide-bond-cleaving residue (Spr) in which the stimuli available for the main chain cleavage vary according to the choice of protecting groups on the residue. In this review, design and synthesis of Spr are introduced, and challenges to apply Spr to other fields to enable, for example, functional control, localization control, delivery of cargos, labeling of a protein of interest in living cells, and identification of target proteins of bioactive ligands are discussed. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.
(徳島大学機関リポジトリ): ● Metadata: 111930
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/psc.2961
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28105728; ● Search Scopus @ Elsevier (PMID): 28105728; ● Search Scopus @ Elsevier (DOI): 10.1002/psc.2961

(徳島大学機関リポジトリ: 111930, DOI: 10.1002/psc.2961, PubMed: 28105728) 津田雄介, 重永章, 佐藤浩平, 中村太寛, 北風圭介, 猪熊翼, 伊藤孝司, 大髙章 :
天然アミノ酸配列に適用可能な新規タンパク質チオエステル合成法の開発,
ケミカルバイオロジー, Vol.9, 7-10, 2016年6月. Akira Otaka, Kohei Sato and Akira Shigenaga :
Chemical synthesis of proteins using N-sulfanylethylanilide peptides, based on N-S acyl transfer chemistry,
Topics in Current Chemistry, Vol.363, 33-56, May 2015.

(要約): Native chemical ligation (NCL), which features the use of peptide thioesters, is among the most reliable ligation protocols in chemical protein synthesis. Thioesters have conventionally been synthesized using tert-butyloxycarbonyl (Boc)-based solid-phase peptide synthesis (SPPS); however, the increasing use of 9-fluorenylmethyloxycarbonyl (Fmoc) SPPS requires an efficient preparative protocol for thioesters which is fully compatible with Fmoc chemistry. We have addressed this issue by mimicking the naturally occurring thioester-forming step seen in intein-mediated protein splicing of the intein-extein system, using an appropriate chemical device to induce N-S acyl transfer reaction, avoiding the problems associated with Fmoc strategies. We have developed N-sulfanylethylanilide (SEAlide) peptides, which can be synthesized by standard Fmoc SPPS and converted to the corresponding thioesters through treatment under acidic conditions. Extensive examination of SEAlide peptides showed that the amide-type SEAlide peptides can be directly and efficiently involved in NCL via thioester species in the presence of phosphate salts, even under neutral conditions. The presence or absence of phosphate salts provided kinetically controllable chemoselectivity in NCL for SEAlide peptides. This allowed SEAlide peptides to be used in both one-pot/N-to-C-directed sequential NCL under kinetically controlled conditions, and the convergent coupling of large peptide fragments, which facilitated the chemical synthesis of proteins over about 100 residues. The use of SEAlide peptides, enabling sequential NCL operated under kinetically controlled conditions, and the convergent coupling, were used for the total chemical synthesis of a 162-residue monoglycosylated GM2-activator protein (GM2AP) analog.
(出版サイトへのリンク): ● Publication site (DOI): 10.1007/128_2014_586
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25467538; ● Search Scopus @ Elsevier (PMID): 25467538; ● Search Scopus @ Elsevier (DOI): 10.1007/128_2014_586

(DOI: 10.1007/128_2014_586, PubMed: 25467538) 中村太寛, 佐藤浩平, 大髙章 :
タンパク性医薬品開発に向けたペプチド化学,
化学工業(特集ペプチド化学の新潮流(1)), Vol.65, No.11, 842-848, 2014年11月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1521417754728344960

(CiNii: 1521417754728344960) 重永章, 大髙章 :
刺激応答型アミノ酸の開発と生命科学分野への展開,
化学工業(特集ペプチド化学の新潮流(1)), Vol.65, No.11, 849-856, 2014年11月.

(徳島大学機関リポジトリ): ● Metadata: 111953
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1050583647830216832

(徳島大学機関リポジトリ: 111953, CiNii: 1050583647830216832) 佐藤浩平, 大髙章 :
ペプチド・タンパク質を基盤とする創薬展開への化学基盤の開拓,
化学工業, Vol.65, No.6, 411-417, 2014年6月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1521136280904574080

(CiNii: 1521136280904574080) 傳田将也, 山本純, 佐藤浩平, 坂本健, 重永章, 佐藤陽一, 吉村好之, 山内あい子, 大髙章 :
新規タンパク質選択的ラベル化試薬''SEAL-tag''の開発研究,
ケミカルバイオロジー, Vol.6, 6-9, 2013年6月. 大髙章 :
情報発信型人工タンパク質創製に向けた有機・生物有機化学的挑戦,
有機合成化学協会誌, Vol.70, No.10, 1054, 2012年10月.

(要約): Functional analyses of endogenous proteins represent indispensable steps for development of drugs for the protein targets. Here, informative-function-incorporated artificial proteins corresponding to the targets should serve as a useful molecular device for evaluating the naturally occurring proteins as a potential drug target. Chemical synthesis and chemical manipulation of proteins allow such artificial proteins to be prepared. We therefore developed a facile synthetic protocol for proteins and a chemical device for functional change of proteins. In this review are addressed both N-sulfanylethylanilide (SEAlide) peptides for protein synthesis and stimulus-responsive amino acids for the functional conversion. SEAlide peptides were initially developed as peptide thioester precursors obtainable by 9-fluorenylmethyloxycarbonyl (Fmoc) solid-phase peptide synthesis. Investigation on the SEAlide peptides uncovered that a one-pot/multi-fragment sequential native chemical ligation (NCL) is achieved efficiently using the SEAlide unit to give proteins. For functional change of proteins, stimulus-responsive amino acids were developed. Upon responding to various stimuli, the newly developed amino acid-containing peptides are spliced into two peptide parts. Combination of the splicing reaction and an acyl-transfer chemistry allows the function of peptide to be changed.
(キーワード): protein synthesis / native chemical ligation / N-S acyl transfer / thioester / peptide bond cleavage / stimulus-responsive amino acid
(出版サイトへのリンク): ● Publication site (DOI): 10.5059/yukigoseikyokaishi.70.1054
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282680316668032; ● Search Scopus @ Elsevier (DOI): 10.5059/yukigoseikyokaishi.70.1054

(DOI: 10.5059/yukigoseikyokaishi.70.1054, CiNii: 1390282680316668032) Akira Otaka, Kohei Sato, Hao Ding and Akira Shigenaga :
One-pot/sequential native chemical ligation using N-sulfanylethylanilide peptide,
Chemical Record, Vol.12, No.5, 479-490, Aug. 2012.

(要約): N-Sulfanylethylanilide (SEAlide) peptides were developed with the aim of achieving facile synthesis of peptide thioesters by 9-fluorenylmethyloxycarbonyl (Fmoc)-based solid-phase peptide synthesis (Fmoc SPPS). Initially, SEAlide peptides were found to be converted to the corresponding peptide thioesters under acidic conditions. However, the SEAlide moiety was proved to function as a thioester in the presence of phosphate salts and to participate in native chemical ligation (NCL) with N-terminal cysteinyl peptides, and this has served as a powerful protein synthesis methodology. The reactivity of a SEAlide peptide (anilide vs. thioester) can be easily tuned with or without the use of phosphate salts. This interesting property of SEAlide peptides allows sequential three-fragment or unprecedented four-fragment ligation for efficient one-pot peptide/protein synthesis. Furthermore, dual-kinetically controlled ligation, which enables three peptide fragments simultaneously present in the reaction to be ligated in the correct order, was first achieved using a SEAlide peptide. Beyond our initial expectations, SEAlide peptides have served in protein chemistry fields as very useful crypto-peptide thioesters.
(キーワード): Cysteine / Esters / Oxazolidinones / Peptides / Sulfhydryl Compounds
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/tcr.201200007
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22927228; ● Search Scopus @ Elsevier (PMID): 22927228; ● Search Scopus @ Elsevier (DOI): 10.1002/tcr.201200007

(DOI: 10.1002/tcr.201200007, PubMed: 22927228) 重永章, 佐藤浩平, 大髙章 :
ペプチドチオエステル合成法の最近の進展,
有機合成化学協会誌, Vol.68, No.9, 911-919, 2010年9月.

(要約): Investigations of biological processes by using peptide, protein, or its derivative are undoubtedly valuable. In this field, chemical synthesis of native or modified peptides/proteins is indispensable. Fragment condensation strategy, such as thioester method or native chemical ligation, is widely used for chemical synthesis of large peptides and proteins. C-Terminal peptide/protein thioesters have been used as building blocks for the fragment condensation strategy. Therefore, development of methodologies for preparing C-terminal peptide/protein thioesters is one of the most attracting theme in recent peptide/protein chemistry field. In this review, the methodologies for preparing C-terminal peptide/protein thioesters utilizing chemistry, biochemistry, or gene engineering are summarized.
(キーワード): acyl transfer / expressed protein ligation / fragment condensation / native chemical ligation / peptide thioester / peptide synthesis / protein thioester / protein synthesis / thioester method
(出版サイトへのリンク): ● Publication site (DOI): 10.5059/yukigoseikyokaishi.68.911
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390001205312881408; ● Search Scopus @ Elsevier (DOI): 10.5059/yukigoseikyokaishi.68.911

(DOI: 10.5059/yukigoseikyokaishi.68.911, CiNii: 1390001205312881408) 重永章, 佐藤浩平, 大髙章 :
十字路:セーフティーキャッチリンカー,
有機合成化学協会誌, Vol.68, No.9, 973, 2010年9月.

(出版サイトへのリンク): ● Publication site (DOI): 10.5059/yukigoseikyokaishi.68.973
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282680287568896; ● Search Scopus @ Elsevier (DOI): 10.5059/yukigoseikyokaishi.68.973

(DOI: 10.5059/yukigoseikyokaishi.68.973, CiNii: 1390282680287568896) 重永章, 大髙章 :
磁気浮上を利用した簡便な固相反応モニター法の開発,
ケミカルバイオロジー, Vol.2, 13, 2009年5月.

(徳島大学機関リポジトリ): ● Metadata: 116114

(徳島大学機関リポジトリ: 116114) 大石真也, 鳴海哲夫, 大野浩章, 大髙章, 藤井信孝 :
アルケン型ジペプチドイソスターの合成法の開発と生理活性ペプチドの構造活性相関研究への応用,
有機合成化学協会誌, Vol.66, No.9, 846-857, 2008年9月.

(要約): Peptide bonds are one of the essential contributors to overall structure and functions of bioactive peptides. The partial double-bond character derived from the resonance structure restricts the free rotation of the carbon-nitrogen bond and stabilizes the planar conformations. Additionally, the ability to form hydrogen bonds allows the stabilization of characteristic secondary structures such as α-helix and β-turn as well as the association with the receptors. Alkene dipeptide isosteres, based on the concept of ω-dihedral angle planarity, have been used as amide bond equivalents, which serve as mechanistic probes lacking amide polarity. We have developed a facile methodology for the stereoselective synthesis of highly functional dipeptide isosteres. The key reaction is the alkylation of δ-aminated α, β-enoates having an appropriate leaving group at the γ-position. Organocopper-mediated anti-SN2' alkylation of α, β-enoates afforded multi-substituted olefin-containing isosteres. One-pot reduction-transmetalation-alkylation of γ, γ-difluoro-α, β-enoates provided fluoroalkene dipeptide isosteres. Reduction of these substrates with organocuprate, SmI2, or Pd/PhSiH3/Et3N system gave Xaa-Gly-type mimetics. Similar methods were also utilized for the preparation of cis-peptide bond mimetics. The resulting isosteres and the key intermediates were studied in structure-activity relationship of bioactive peptides including integrin αvβ3 antagonist, chemokine receptor CXCR 4 antagonist, puberty-related GPR 54 agonist, and peptide transporter PEPT1 substrate.
(キーワード): organocopper-mediated alkylation / transmetalation / bioactive peptide / peptidomimetic / alkene dipeptide isostere / structure-activity relationship / integrin / αVβ3 / chemokine / CXCR4 / kisspeptin / GPR54 / peptide transporter / PEPT1
(出版サイトへのリンク): ● Publication site (DOI): 10.5059/yukigoseikyokaishi.66.846
(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1390282680288398720; ● Summary page in Scopus @ Elsevier: 2-s2.0-57049119193

(DOI: 10.5059/yukigoseikyokaishi.66.846, CiNii: 1390282680288398720, Elsevier: Scopus) 重永章, 辻大輔, 西岡直美, 津田修吾, 伊藤孝司, 大髙章 :
刺激応答型アミノ酸を利用した核-細胞質シャトルペプチドの開発,
ケミカルバイオロジー, Vol.1, No.1, 7-10, 2008年5月. 重永章, 大髙章 :
Split and Pool法を用いたOne-bead, One-peptideライブラリーの構築とハイスループットスクリーニングへの展開,
蛋白質核酸酵素, Vol.52, No.13 Suppl, 1792-1793, 2007年10月.

(キーワード): Binding Sites / Combinatorial Chemistry Techniques / Drug Design / Ligands / Peptide Library / Peptides
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18051429; ● Summary page in Scopus @ Elsevier: 2-s2.0-38449088482

(PubMed: 18051429, Elsevier: Scopus) 藤井信孝, 大石真也, 大髙章 :
プロテオミクスを基盤とするケミカルバイオロジー -情報から制御へ,
Bionics, Vol.3, No.10, 46-51, 2006年10月. 大髙章, 藤井信孝 :
膜融合阻害性抗ウイルスペプチドの開発,
化学工業, Vol.57, No.10, 797-801, 2006年10月.

(文献検索サイトへのリンク): ● CiNii @ 国立情報学研究所 (CRID): 1523106604538391680

(CiNii: 1523106604538391680) 藤井信孝, 大髙章, 玉村啓和 :
ケミカルプロテオミックス先導型創薬基盤の革新,
細胞工学, Vol.15, No.11, 1181-1186, 2005年11月. 西川裕輝, 藤井信孝, 大髙章 :
抗SARS-CoV活性ペプチドの創製研究,
Med. Chem. News, Vol.15, 18-23, 2005年. 大髙章, 藤井信孝, 山本直樹 :
SARS治療薬の展望,
現代医療, Vol.36, No.11, 64-51, 2004年11月. Akira Otaka, Etsuko Mitsuyama, Junko Watanabe, Hideaki Watanabe and Nobutaka Fujii :
Synthesis of fluorine-containing bioisosteres corresponding to phosphoamino acids and dipeptide units,
Biopolymers, Vol.76, No.2, 140-149, 2004.

(要約): It has been shown that fluorinated analogues of naturally occurring biological active compounds including amino acids often exhibit unique physiological activity. Among wide varieties of fluorine-containing amino acids, nonhydrolyzable phosphoamino acids possessing a substituent of the difluoromethylene (CF(2)) unit for the phosphoryl ester oxygen are of value in the medicinal and biological fields. We have engaged in the synthesis of these classes of nonhydrolyzable phosphoamino acids corresponding to pTyr 3, pSer 4, and pThr 5 with their incorporation into peptides using newly developed deprotecting procedures. In this article, stereoselective synthesis of the CF(2)-substituted pThr mimetics and development of a two-step deprotecting methodology for the nonhydrolyzable analogues are reviewed. In the course of the above synthetic study, we found that gamma,gamma-difluoro-alpha,beta-enoates were reduced to gamma-fluoro-beta,gamma-enoates by organocopper reagents and then applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres, which have served as potential dipeptide mimetics having structural as well as electrostatic similarity to the parent peptide bonds. Furthermore, mechanistic investigation of the organocopper-mediated reduction led us to development of a SmI(2)-mediated approach toward the synthesis of the fluoroalkene isosteres.
(キーワード): Biomimetic Materials / Dipeptides / Hydrocarbons, Fluorinated / Phosphoamino Acids
(出版サイトへのリンク): ● Publication site (DOI): 10.1002/bip.10570
(文献検索サイトへのリンク): ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15054894; ● Search Scopus @ Elsevier (PMID): 15054894; ● Search Scopus @ Elsevier (DOI): 10.1002/bip.10570

(DOI: 10.1002/bip.10570, PubMed: 15054894) 大髙章 :
高付加価値ペプチド合成のための最終脱保護法の開発と細胞内情報伝達機構解明への展開研究,
薬学雑誌, Vol.120, 54-67, 2000年. 大髙章, 相本三郎 :
構造生物学の方法論の新しい展開, --- リン酸化ペプチドの化学合成 ---,
蛋白質核酸酵素, Vol.44, 302-309, 1999年. 大髙章, 藤井信孝 :
ジスルフィド結合形成材,
有機合成化学協会誌, Vol.48, 1010-1011, 1990年11月. 大髙章, 藤井信孝 :
ペプチド合成における最終脱保護材,
有機合成化学協会誌, Vol.48, 1044-1045, 1990年11月. 大髙章, 藤井信孝 :
シスチン含有ペプチドの新規合成法,
有機合成化学協会誌, Vol.48, 658-671, 1990年7月.

講演・発表

SATOH Daiki, Chiho Shinozaki, Masaya Denda and Akira Otaka :
Development of late-stage acylation methodology of threonine residue enabled by chemoselective acyl transfer followed by desulfurization,
37th European Peptide Symposium 14th International Peptide Symposium, Firenze, Aug. 2024. Kohta Hidaka, Daishiro Kobayashi, JUNYA Hayashi, Masaya Denda and Akira Otaka :
Disulfide-shuffling encountered in insulin synthesis using disulfide-forming reaction enabled by S-protected cysteine and sulfoxide pair,
9th Chemical Protein Synthesis Conference, Nagoya, Jun. 2024. JUNYA Hayashi, Daishiro Kobayashi, Masaya Denda and Akira Otaka :
Development of α-thioetherification reaction on peptides for sactipeptide synthesis using glycyl hydroxamic acid,
9th Chemical Protein Synthesis Conference, Nagoya, Jun. 2024. SATOH Daiki, Chiho Shinozaki, Masaya Denda and Akira Otaka :
Development of acylation protocol of threonine residue by sequential highly efficient acyl transfersdesulfurization,
9th Chemical Protein Synthesis Conference, Nagoya, Jun. 2024. Akira Otaka, Kohta Hidaka, Daishiro Kobayashi, JUNYA Hayashi and Masaya Denda :
Insulin Synthesis Using Stepwise Disulfide Bond Formation Enabled by S-Protected Cysteine and Cysteine Sulfoxide Pairs,
9th Chemical Protein Synthesis Conference, Nagoya, Jun. 2024. Daishiro Kobayashi, Masaya Denda and Akira Otaka :
S-Protected cysteine sulfoxide-enabled peptide and protein customization methodology,
Biologics 2024, London, Mar. 2024. Kohta Hidaka, Daishiro Kobayashi, JUNYA Hayashi, OHKAWACHI Kento, Masaya Denda and Akira Otaka :
DEVELOPMENT OF ONE-POT/STEPWISE DISULFIDE BOND-FORMING REACTION ENABLED BY S-PROTECTED CYSTEINE SULFOXIDE WITH ITS APPLICATION TO SYNTHESIS OF INSULIN AND ITS LIPIDATED ANALOGUE,
13th International Peptide Symposium 15th Australian Peptide Conference, Brisbane, Oct. 2023. JUNYA Hayashi, Daishiro Kobayashi, Masaya Denda and Akira Otaka :
DEVELOPMENT OF OXIDANT FREE METHODOLOGY FOR PREPARING N-GLYOXYLYL PEPTIDE AND ITS APPRICATIONS,
13th International Peptide Symposium 15th Australian Peptide Conference, Brisbane, Oct. 2023. Daishiro Kobayashi, JUNYA Hayashi, Kohta Hidaka, OHKAWACHI Kento, Yutaka Kohmura, Masaya Denda and Akira Otaka :
Protein tryptophan modification enabled by using S-protected cysteine sulfoxide under mild acid conditions,
13th International Peptide Symposium 15th Australian Peptide Conference, Brisbane, Oct. 2023. Mika Ohhira, OHKAWACHI Kento, Kaito Anzaki, Mina Hojo, Sayaka Tani, Masaya Denda, Hitoshi Mizuguchi and Akira Otaka :
Development of synthetic method for synthesizing di-Tyr-containing bi-aryl peptides enabled by oxidation of sulfenyl Tyr,
AIMECS 2023, Seoul, Jun. 2023. Chiho Shinozaki, Yutaka Kohmura, Tetsuro Yoshimaru, Tsuyoshi Tahara, Masaya Denda, Hidefumi Mukai, Kohta Mohri, Yi Long Chen, Toyomasa Katagiri and Akira Otaka :
Study on a lipidated anti-cancer peptide allowing long-lasting duration in mice model,
AIMECS 2023, Seoul, Jun. 2023. Akira Otaka, OHKAWACHI Kento, Kaito Anzaki and Masaya Denda :
Tyr- or Trp-selective CH sulfenylation enabled by acid- activated S-acetamidomethyl cysteine sulfoxide,
19th Akabori Conference German-Japanese Symposium on Peptide Science, 大津市, May 2023. Akira Otaka :
Development of Desulfurization-compatible New Thiol Catalyst for Native Chemical Ligation,
18th Akabori Conference German-Japanese Symposium on Peptide Science, Online, Mar. 2021. Naoto Naruse, Daishiroh Kobayashi, Akira Shigenaga and Akira Otaka :
Copper-mediated Ring Opening of Thiazolidine Derivative for Protein Chemical Synthesis,
27th International Society of Heterocyclic Chemistry Congress, Kyoto, Sep. 2019. Naoto Naruse, Daishiroh Kobayashi, Kento Ohkawachi, Akira Shigenaga and Akira Otaka :
Development of Novel Ring-Opening Reaction of N-Terminal Thiazolidine for Chemical Protein Synthesis,
26th American Peptide Symposium/11th International Peptide Symposium, Monterey, CA, USA, Jun. 2019. Akira Shigenaga, Takuya Morisaki, Taiki Kohiki, Masaya Denda, Tsubasa Inokuma and Akira Otaka :
Development of acyl transfer-based chemical biology tools for purification/selective labeling of target proteins,
5th International Symposium for Medicinal Sciences, Chiba, Mar. 2019. Taiki Kohiki, Yusuke Kato, Masaya Denda, Yusuke Nishikawa, Kazuko YORITA, Ikuko Sagawa, Tsubasa Inokuma, Akira Shigenaga, Kiyoshi Fukui and Akira Otaka :
Development and application of novel protein labeling reagent "SEAL",
10th International Peptide Symposium, Kyoto, Dec. 2018. Kento Ohkawachi, Kyohei Morimoto, Naoto Naruse, Kenzo Yamatsugu, Akira Shigenaga, Motomu Kanai and Akira Otaka :
Development of methodology for cyclic peptide synthesis using a thiol-incorporated DMAP catalyst,
10th International Peptide Symposium, Kyoto, Dec. 2018. Keitaroh Anyohji, Keisuke Aihara, Tetsuro Yoshimaru, Akira Shigenaga, Toyomasa Katagiri and Akira Otaka :
Development of anti-cancer peptide based on prohibitin 2,
10th International Peptide Symposium, Kyoto, Dec. 2018. Naoto Naruse, Kiyoka Matsumoto, Akira Shigenaga and Akira Otaka :
Development of method for deprotection of N-terminal thiazolidine derivative using copper salt for chemical protein synthesis,
10th International Peptide Symposium, Kyoto, Dec. 2018. Chiaki Komiya, Jun Tsukimoto, Masahiro Ueda, Takuya Morisaki, Tsubasa Inokuma, Akira Shigenaga, Kouji Itou and Akira Otaka :
Preparation of protein thioesters enabled by carboxypeptidase-mediated C-terminal specific hydrazinolysis,
10th International Peptide Symposium, Kyoto, Dec. 2018. Yusuke Kato, Nobuo Maita, Taiki Kohiki, Sumire Kurosawa, Yusuke Nishikawa, Ikuko Sagawa, Masaya Denda, Tsubasa Inokuma, Yuji Shishido, Kazuko YORITA, Akira Shigenaga, Akira Otaka and Kiyoshi Fukui :
Combined approach of computation and enzymology to investigate novel D-amino acid oxidase inhibitors,
The 13th International Symposium of the Institute Network for Biomedical Sciences joint with the 3rd Symposium of the Inter-University Research Network for Trans-Omics Medicine and the 28th Hot Spring Harbor Symposium, Fukuoka, Oct. 2018. Tsubasa Inokuma, Nishida Kodai, Akira Shigenaga, Ken-ichi Yamada and Akira Otaka :
Novel methodology for the synthesis of-indolyl-glycine containing peptidevia direct asymmetric FriedelCrafts reactionto peptidyl imine,
35th European Peptide Symposium, Dublin, Ireland, Aug. 2018. Yusuke Kato, Taiki Kohiki, Yusuke Nishikawa, Ikuko Sagawa, Masaya Denda, Tsubasa Inokuma, Yuji Shishido, Akira Shigenaga, Akira Otaka and Kiyoshi Fukui :
Studies on binding molecules to D-amino acid oxidase using computational approaches,
The 12th International Symposium of the Institute Network, Tokyo, Nov. 2017. Akira Otaka :
Development of anti-breast cancer stapled peptides targeting BIG3-PHB2 interaction,
AIMECS 2017, Melbourne, Australia, Jul. 2017. Kazuko YORITA, Sumire Kurosawa, Yuri Yoshida, Yoshiki Kashiwada, Shigeki Sano, Akira Otaka and Kiyoshi Fukui :
Screening of the effectors for human D-amino acid oxidase and the analyses of structure-activity relationships,
The 19th triennial International Symposium on Flavins and Flavoproteins, Groningen, Jul. 2017. Akira Otaka :
Application of N-Sulfanylethylanilide(SEAlide) Unit to Protein Chemical Synthesis and Protein Enrichment,
American Peptide Symposium 2017, Whistler, BC, Canada, Jun. 2017. Takuya Morisaki, Masaya Denda, Jun Yamamoto, Daisuke Tsuji, Tsubasa Inokuma, Kouji Itou, Akira Shigenaga and Akira Otaka :
Development of N-Sulfanylethylanilide-based Traceable Linker for Purification and Selective Labeling of Target Proteins,
American Peptide Symposium 2017, Whistler, BC, Canada, Jun. 2017. Naoto Naruse, Kento Ohkawachi, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Development of methodology for preparation of peptide thioester via on-resin N-S acyl transfer using N-sulfanylethylanilide peptide,
American Peptide Symposium 2017, Whistler, BC, Canada, Jun. 2017. Akira Otaka, Keisuke Aihara, Tetsuro Yoshimaru, Akira Shigenaga and Toyomasa Katagiri :
Development of long-lasting stapled peptides targeting BIG3-PHB2 interaction in breast cancer cells,
The 6th Pharmaceutical Sciences World Congress 2017, Stockholm, May 2017. Koichiro Tsuchiya, Aihara Haruna, Xu Wenting, Jin Meina, Tomida Yosuke, Yamaoka Tomomi, Naonobu Tanaka, Yasumasa Ikeda, Akira Shigenaga, Akira Otaka, Toshiaki Tamaki, Yoshiki Kashiwada and Koichiro Tsuchiya :
A limonene-derivative from Sudachi peel activates sirt1 and improves lipid and glucose metabolism in high fat diet-fed mice.,
欧州糖尿病学会, Dec. 2016. Takahiko Hara, Kosuke Tanegashima, Rena Takahashi, Hideko Nuriya, Naoto Naruse, Kohei Tsuji, Akira Shigenaga and Akira Otaka :
A Novel Function of a CXC-type Chemokine CXCL14 as a Specific Carrier of CpG DNA into Dendritic Cells for Activating Toll-like Receptor 9-mediated Adaptive Immunity,
58th ASH Annual Meeting & Exposition, San Diego, Dec. 2016. Takahiro Nakamura, Akira Shigenaga, Naoto Naruse, Tsubasa Inokuma, Kouji Itou and Akira Otaka :
Second-Generation Synthetic Strategy of GM2-Activator Protein (GM2AP) Analogues Applicable to the Preparation of a Protein Library,
34th European Peptide Symposium 2016 & 8th International Peptide Symposium, Leipzig, Germany, Sep. 2016. Chiaki Komiya, Keisuke Aihara, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Intein-inspired Amide Bond Processing Device,
34th European Peptide Symposium 2016 & 8th International Peptide Symposium, Leipzig, Germany, Sep. 2016. Keisuke Aihara, Kosuke Yamaoka, Naoto Naruse, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
One-Pot/Sequential Native Chemical Ligation Using Photo-responsive Crypto-thioester,
34th European Peptide Symposium 2016 & 8th International Peptide Symposium, Leipzig, Germany, Sep. 2016. Akira Otaka, Rin Miyajima, Yusuke Tsuda and Akira Shigenaga :
Regioselective S-Cyanylation-mediated Preparation of Peptide Thioester,
16th Akabori Conference Japanese-German Symposium on Peptide Science, Kobe, May 2016. Kosuke Tanegashima, Rena Takahashi, Hideko Nuriya, Kohei Tsuji, Akira Shigenaga, Akira Otaka and Takahiko Hara :
A CXC type chemokine CXCL14 directly binds to CpG-C DNA to activate Toll-like receptor 9 signaling,
Nucleic Acid Sensing Pathways: Innate Immunity, Immunobiology and Therapeutics (E2), Dresden, May 2016. Akira Otaka :
N-Sulfanylethylanilide peptide as a crypto thioester for protein chemical synthesis,
5th Modern Solid Phase Peptide Synthesis & Its Application Symposium, Queensland (Australia), Oct. 2015. 宮本理人, 粟飯原遥奈, Wenting Xu, Meina Jin, 冨田洋介, 山岡朋美, 田中直伸, 池田康将, 重永章, 大髙章, 玉置俊晃, 柏田良樹, 土屋浩一郎 :
リモネン誘導体によるsirt1活性化を介した脂質低下作用,
日本肥満学会，アジアオセアニア糖尿病学会, 名古屋, 2015年10月. Yusuke Tsuda, Akira Shigenaga, Kohei Tsuji, Masaya Denda, Kohei Sato, Keisuke Kitakaze, Takahiro Nakamura, Tsubasa Inokuma, Kouji Itou and Akira Otaka :
Development of Chemistry-based Protocol for Sequence-dependent Thioesterification,
American Peptide Symposium 2015, Florida, Jun. 2015. Masaya Denda, Takuya Morisaki, Jun Yamamoto, Kohei Sato, Tsubasa Inokuma, Youichi Sato, Aiko Yamauchi, Akira Shigenaga and Akira Otaka :
In Cell Labeling of Target Proteins using ''SEAL-tag'',
American Peptide Symposium 2015, Florida, Jun. 2015. Licht Miyamoto, Haruna Aihara, Wenting Xu, Meina Jin, Yosuke Tomida, Tomomi Yamaoka, Naonobu Tanaka, Yasumasa Ikeda, Akira Shigenaga, Akira Otaka, Toshiaki Tamaki, Yoshiki Kashiwada and Koichiro Tsuchiya :
Limonene-derivative Ameliorates Lipid Profiles by Upregulation of Sirt1 Activity and Expression in Cultured Cells and High Fat Diet-Fed Mice,
American diabetes association, Boston, Jun. 2015. Akira Shigenaga, Kohei Sato, Tsubasa Inokuma and Akira Otaka :
Chemical protein synthesis utilizing SEAlide technology that is potentially applicable to incorporation of artificial amino acids into proteins for their functional control,
The 2nd International Symposium on Fusion Materials Program, Tokyo, Nov. 2014. Akira Otaka, Yusuke Tsuda and Akira Shigenaga :
Chemical thioester synthesis applicable to naturally occurring peptide sequence,
15th Akabori Conference Japanese-German Symposium on Peptide Science, Boppard, Sep. 2014. Kohei Tsuji, Kosuke Tanegashima, Akira Shigenaga, Takahiko Hara and Akira Otaka :
Dimerized CXCL14 C-terminal regions inhibit CXCL12-CXCR4 signaling axis,
The 33rd European Peptide Symposium, Sofia, Aug. 2014. Kohei Sato, Keisuke Kitakaze, Ken Sakamoto, Akira Shigenaga, Daisuke Tsuji, Kouji Itou and Akira Otaka :
Synthetic study of GM2 activator protein using N-sulfanylethylanilide peptide,
The 33rd European Peptide Symposium, Sofia, Aug. 2014. Yusuke Tsuda, Akira Shigenaga, Kohei Sato, Takahiro Nakamura, Keisuke Kitakaze, Kouji Itou and Akira Otaka :
Development of chemical protocol for preparation of peptide/protein thioesters applicable to naturally occurring sequences,
17th KPPS Annual Symposium, Seoul, Nov. 2013. Jun Yamamoto, Miku Kita, Akira Shigenaga, Youichi Sato, Aiko Yamauchi and Akira Otaka :
Development of thiol-responsive traceable linker for efficient enrichment and selective labeling of target proteins,
4th Asia-Pacific International Peptide Symposium, 50th Japanese Peptide Symposium, Suita, Nov. 2013. Keisuke Aihara, Akira Shigenaga, Daisuke Takahashi and Akira Otaka :
New approach for synthesis of lactam bridged peptides using olefin metathesis on AJIPHASE®,
4th Asia-Pacific International Peptide Symposium, 50th Japanese Peptide Symposium, Suita, Nov. 2013. Miku Kita, Jun Yamamoto, Koji Ebisuno, Chiaki Komiya, Akira Shigenaga, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Akira Otaka :
Development of hydrogen peroxide-responsive amide bond cleavage device,
4th Asia-Pacific International Peptide Symposium, 50th Japanese Peptide Symposium, Suita, Nov. 2013. Yusuke Tsuda, Akira Shigenaga, Kohei Sato, Takahiro Nakamura and Akira Otaka :
Development of Chemical Protocols for Producing Peptide Thioesters from Naturally Occurring Peptide Sequences, Part 1,
4th Asia-Pacific International Peptide Symposium, 50th Japanese Peptide Symposium, Suita, Nov. 2013. Yusuke Tsuda, Akira Shigenaga, Kohei Sato, Rin Miyajima and Akira Otaka :
Development of Chemical Protocols for Producing Peptide Thioesters from Naturally Occurring Peptide Sequences, Part 2,
4th Asia-Pacific International Peptide Symposium, 50th Japanese Peptide Symposium, Suita, Nov. 2013. Takahiro Nakamura, Akira Shigenaga, Kohei Sato, Yusuke Tsuda and Akira Otaka :
Application of peptidyl prolyl thioesters to native chemical ligation,
4th Asia-Pacific International Peptide Symposium, 50th Japanese Peptide Symposium, Suita, Nov. 2013. Keisuke Aihara, Daisuke Takahashi, Akira Shigenaga and Akira Otaka :
Olefin metathesis approach utilizing AJIPHASE(R) for the synthesis of lactam bridged peptides,
4th Modern Solid Phase Peptide Synthesis & Its Application Symposium, Kobe, Nov. 2013. Ken Sakamoto, Kohei Sato, Akira Shigenaga and Akira Otaka :
Development of practical synthetic method for Fmoc amino acid-incorporated N-sulfanylethyl anilide linker as peptide thioester equivalent,
4th Modern Solid Phase Peptide Synthesis & Its Application Symposium, Kobe, Nov. 2013. Jun Yamamoto, Miku Kita, Akira Shigenaga, Youichi Sato, Aiko Yamauchi and Akira Otaka :
Application of thiol-responsive amino acid to traceable linker for purification and selective labeling of target protein,
23rd American Peptide Symposium, Hawai'i, Jun. 2013. Keisuke Aihara, Kohei Tsuji, Akira Shigenaga and Akira Otaka :
Ring-closing metathesis approach for the synthesis of Lys-Glu bridged cyclic peptides,
23rd American Peptide Symposium, Hawai'i, Jun. 2013. Ken Sakamoto, Kohei Sato, Akira Shigenaga, Daisuke Tsuji, Kouji Itou and Akira Otaka :
Development of efficient synthetic method for N-amino acyl N-sulfanylethyl anilide linkers as peptide thioester equivalent,
23rd American Peptide Symposium, Hawai'i, Jun. 2013. Akira Otaka :
Development of "Tracable Linkerfor" Protein Idebtification Using Stimulus-responsive Amino Acid,
The 1st International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity, Kyoto, Oct. 2012. Masaya Denda, Jun Yamamoto, Kohei Sato, Ken Sakamoto, Akira Shigenaga, Youichi Sato, Aiko Yamauchi and Akira Otaka :
Development of a novel chemical probe that enables selective labeling of proteins,
The 1st International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity, Kyoto, Oct. 2012. Akira Otaka, Kohei Sato, Hao Ding and Akira Shigenaga :
N-Sulfanylethylanilide peptide for peptide engineering,
The Sixth Peptide Engineering Meeting, Atlanta, Oct. 2012. Kohei Sato, Keisuke Kitakaze, Ken Sakamoto, Akira Shigenaga, Daisuke Tsuji, Kouji Itou and Akira Otaka :
Chemical synthesis of human GM2 activator protein analog using SEAlide peptide-mediated one-pot multi-fragment condensation,
The 6th Takeda Science Foundation Symposium on PharmaSciences, Suita, Sep. 2012. Kohei Tsuji, Kosuke Tanegashima, Akira Shigenaga, Keisuke Aihara, Masaya Denda, Hao Ding, Takahiko Hara and Akira Otaka :
Development of novel antagonistic peptide for CXCL14 receptor,
The 6th Takeda Science Foundation Symposium on PharmaSciences, Suita, Sep. 2012. Akira Otaka :
Chemical Protein Synthesis Using N-Sulfanylethylanilide Peptide,
The 14th Akabori Conference, Niseko, Japan, Sep. 2012. Akira Otaka :
N-Sulfanylethylanilides as a Versatile Chemical Device for Protein Chemistry,
2012 SNU Symposium on Medicinal Chemistry, Seoul, May 2012. Jun Yamamoto, Tomohiro Tanaka, Masaya Denda, Koji Ebisuno, Akira Shigenaga, Wataru Nomura, Hirokazu Tamamura and Akira Otaka :
Application of Stimulus-responsive Amino Acid to Traceable Linker for Efficient Enrichment and Specific Labeling of Target Proteins,
8th AFMC International Medicinal Chemistry Symposium, Tokyo, Nov. 2011. Kohei Tsuji, Kosuke Tanegashima, Akira Shigenaga, Keisuke Aihara, Hao Ding, Masaya Denda, Takahiko Hara and Akira Otaka :
The First Accomplishment of Development of CXCL14 Antagonistic Peptide by Dimerization of CXCL14 Fragment,
8th AFMC International Medicinal Chemistry Symposium, Tokyo, Nov. 2011. Akira Shigenaga, Masaya Denda, Keiji Ogura, Koji Ebisuno and Akira Otaka :
Development of caged nonhydrolyzable phosphoserine and its incorporation into biomineralization-related peptide,
The 1st International Symposium on Fusion Materials Program, Toba, Oct. 2011. Jun Yamamoto, Tomohiro Tanaka, Masaya Denda, Akira Shigenaga, Wataru Nomura, Hirokazu Tamamura and Akira Otaka :
Design and synthesis of traceable linker for efficient enrichment and specific labeling of target proteins,
22nd American Peptide Symposium, San Diego, Jun. 2011. Kohei Sato, Shugo Tsuda, Kohei Tsuji, Ken Sakamoto, Akira Shigenaga and Akira Otaka :
N-sulfanylethylanilide derivative as a peptide thioester equivalent,
22nd American Peptide Symposium, San Diego, Jun. 2011. Kohei Tsuji, Yoshitake Sumikawa, Kosuke Tanegashima, Akira Shigenaga, Takahiko Hara and Akira Otaka :
Synthesis of CXCL14 and its derivatives utilizing C to N or N to C directive sequential NCL protocol,
22nd American Peptide Symposium, San Diego, Jun. 2011. Akira Otaka and Akira Shigenaga :
Development of amide bond cleavage device with application to chemical biology use,
5th International Peptide Symposium, Kyoto, Dec. 2010. Kohei Tsuji, Yoshitake Sumikawa, Kosuke Tanegashima, Akira Shigenaga, Takahiko Hara and Akira Otaka :
Synthesis and biological evaluation of CXCL14 and its derivatives,
5th International Peptide Symposium in conjunction with 47th Japanese Peptide Symposium, Kyoto, Dec. 2010. Kohei Sato, Shugo Tsuda, Nami Maeda, Masaya Denda, Akira Shigenaga and Akira Otaka :
Native chemical ligation using N-peptidyl anilide as crypto-thioester,
5th International Peptide Symposium in conjunction with 47th Japanese Peptide Symposium, Kyoto, Dec. 2010. Keiji Ogura, Hiroko Hirakawa, Akira Shigenaga and Akira Otaka :
Synthesis of nonhydrolyzable AMPylated amino acid analogues for uncovering the physiological role of AMPylation,
5th International Peptide Symposium in conjunction with 47th Japanese Peptide Symposium, Kyoto, Dec. 2010. Jun Yamamoto, Nami Maeda, Masaya Denda, Akira Shigenaga and Akira Otaka :
Development of Recapturable Cleavable Linker for Efficient Enrichment and Specific Labeling of Target Proteins,
5th International Peptide Symposium in conjunction with 47th Japanese Peptide Symposium, Kyoto, Dec. 2010. Ko Morishita, Keiko Yamaguchi, Hao Ding, Akira Shigenaga, Kenichi Akaji and Akira Otaka :
Development of Stimulus Responsive Thiol Releasng System for Controlling Activity of Cysteine Protease,
5th International Peptide Symposium in conjunction with 47th Japanese Peptide Symposium, Kyoto, Dec. 2010. Akira Shigenaga, Jun Yamamoto, Naomi Nishioka, Masaya Denda and Akira Otaka :
Enantioselective synthesis of stimulus-responsive amino acid via pyrrolidinyl tetrazole catalyzed asymmetric -amination of aldehyde,
5th International Peptide Symposium in conjunction with 47th Japanese Peptide Symposium, Kyoto, Dec. 2010. Akira Otaka and Akira Shigenaga :
Development of peptide bond cleavage device and its application for chemical biology use,
The 13th Akabori Conference, Leipzig, Germany, Sep. 2010. Jun Yamamoto, Akira Shigenaga, Yoshitake Sumikawa, Toshiaki Furuta and Akira Otaka :
Development of near-infrared two-photon excitation responsive peptide bond cleavage device and examination of its photo-reactivity,
3rd Asia-Pacific International Peptide Symposium, Cheju, Nov. 2009. Yoko Yamaki, Akira Shigenaga and Akira Otaka :
Synthesis of fluoroalkene dipeptide isosteres utilizing intramolecular redox reaction catalyzed by N-heterocyclic carbene,
The 12th Japan-Korea Joint Symposium on Drug Design and Development, Sendai, May 2008. Akira Otaka, Akira Shigenaga, Naomi Nishioka, Daisuke Tsuji and Kouji Itou :
Cleavage of peptide bonds for the preparation of functional peptides,
The 12th Japan-Korea Joint Symposium on Drug Design and Development, Sendai, May 2008. Akira Otaka :
Amide bond cleavage for the preparation of functional peptides,
Roche Colorado Corporation Peptide Symposium, Colorado, USA, Colorado, Sep. 2007. Takashi Tsuji, Yoshikazu Sasaki, Keiko Yamaguchi, Akira Shigenaga, Nobutaka Fujii and Akira Otaka :
Synthesis of (Z)-alkene cis-Xaa-Pro type dipeptide isosteres using organocopper-mediated anti-SN2' reactions,
43rd Japanese Peptide Symposium/4th Peptide Engineering Meeting, Yokohama, Nov. 2006. Akira Shigenaga, Saori Shintaku and Akira Otaka :
Development of Photo-responsive Self-processing Peptides,
43rd Japanese Peptide Symposium/4th Peptide Engineering Meeting, Yokohama, Nov. 2006. Akira Otaka, Yusuke Ohta, Akira Shigenaga and Nobutaka Fujii :
Development of Chemical Devices for Chemical Ligations,
The 11th Akabori Conference, Kloster Banz, Germany, Oct. 2006. Yoshikazu Sasaki, Takashi Tsuji, Ayumu Niida, Akira Shigenaga, Nobutaka Fujii and Akira Otaka :
Regio- and Stereoselective Synthesis of (Z)-Alkene cis-Xaa-Pro Dipeptide Mimetics with Organocopper-mediated Anti-SN2' Reactions,
29th European Peptide Symposium, Gdansk, Sep. 2006. Akira Shigenaga, Saori Shintaku and Akira Otaka :
Design, Synthesis and Photo-processing Reaction of Peptides Possessing the External Stimulus-responsive Amino Acid,
29th European Peptide Symposium, Gdansk, Sep. 2006. Akira Shigenaga, Saori Shintaku and Akira Otaka :
Development of Photo-triggered Self-processing Peptides,
ICOB-5 & ISCNP-25 IUPAC International Conference on Biodiversity and Natural Products, Kyoto, Jul. 2006. Yoshikazu Sasaki, Ayumu Niida, Takashi Tsuji, Akira Shigenaga, Nobutaka Fujii and Akira Otaka :
Synthesis of (Z)-alkene-containing Pro dipeptide isosteres corresponding to cis-prolyl peptides,
The 11th Korea-Japan Joint Symposium On Drug Design and Development, Cheju, May 2006. Akira Otaka, Yusuke Ohta, Akira Shigenaga and Nobutaka Fujii :
Preparation of peptide thioester utilizing S-protected oxazolidinone derived from systeine,
The 11th Korea-Japan Joint Symposium On Drug Design and Development, Cheju, May 2006. Akira Otaka :
Development of chemal devices for synthesis of proteins including membrane proteins,
The 6th International Symposium on Peptide and Protein Materials, Gwangju, Korea, Apr. 2006. 笹川大輝, 篠﨑千穂, 傳田将也, 吉丸哲郎, 片桐豊雅, 大髙章 :
アミド型側鎖架橋を有する乳がん増殖抑制ペプチドの改良合成法の開発,
日本薬学会第145年会, 2025年3月. 林隼矢, 傳田将也, 大髙章 :
N-ヒドロキシペプチドを足掛かりとした新規ペプチドフラグメント縮合法の開発,
日本薬学会第145年会, 2025年3月. 稲月勇斗, 辻貴志, 小林大志朗, 林隼矢, 傳田将也, 大髙章 :
Cysteinylprolyl ester を利用した脂肪鎖―薬物複合体からの薬物放出システムの開発研究,
第41回メディシナルケミストリーシンポジウム, 2024年11月. 大髙章 :
失敗の言語化が未来を拓く,
第63回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2024年11月. 大髙章 :
「失敗の言語化」が拓いたペプチド・タンパク質の修飾反応,
東北大学第10回医薬品開発研究センターシンポジウム次世代創薬に向けたアプローチ, 2024年11月. 大髙章 :
世界の歴史を変えた化合物たちとペプチド,
日本ペプチド学会市民フォーラム2024, 2024年11月. Kohta Hidaka, Daishiro Kobayashi, HAYASHI Junya, Masaya Denda and Akira Otaka :
SELENAZOLIDINE AS A DUALLY FUNCTIONING AGGREGATION DISRUPTING UNIT,
第61回ペプチド討論会, Oct. 2024. 永田綱基, 小林大志朗, 傳田将也, 大髙章 :
S-保護CysスルホキシドによるTrp選択的スルフェニル化反応を利用したGIP–GLP-1ヘテロダイマー合成,
創薬懇話会2024 札幌, 2024年6月. 江口亜希, 大川内健人, 大平実佳, 傳田将也, 大髙章 :
人工脂質膜を反応場とした難溶性膜タンパク質化学合成法の開発,
創薬懇話会2024 札幌, 2024年6月. 太田りか, 左東大輝, 傳田将也, 大髙章 :
新規スレオニン側鎖アシル化法を用いた刺激応答性機能変換ペプチドの合成,
日本ケミカルバイオロジー学会第18回年会, 2024年5月. 林隼矢, 小林大志朗, 傳田将也, 大髙章 :
主鎖アミド保護基を活用したLossen転位反応による合成後期ペプチドα位ヘテロ化法の開発,
日本薬学会第144年会, 2024年3月. 東山晃子, 大西朗人, 柳川瞬矢, 清良尚史, W John Regan, 大川内健人, 傳田将也, 福島圭穣, 西野耕平, 大髙章, 小迫英尊, 藤野裕道 :
EP4受容体の細胞内第3ループ領域に相互作用する因子の探索,
日本薬学会第144年会,横浜,2024年3月29日, 2024年. 篠﨑千穂, 光村豊, 吉丸哲郎, 傳田将也, 片桐豊雅, 大髙章 :
脂肪酸修飾型乳がん増殖抑制ペプチドの開発,
第40回メディシナルケミストリーシンポジウム, 2023年11月. 日高功太, 小林大志朗, 林隼矢, 大川内健人, 傳田将也, 大髙章 :
脂肪鎖修飾型インスリン誘導体合成を指向したS-保護システインスルホキシドを利用したワンポットジスルフィド形成/脂肪酸修飾法の開発,
第40回メディシナルケミストリーシンポジウム, 2023年11月. Akira Otaka :
Side reaction-inspired peptide and protein chemistry,
第60回ペプチド討論会日本ペプチド学会「学会賞」受賞講演, Nov. 2023. Kohta Hidaka, Daishiro Kobayashi, JUNYA Hayashi, OHKAWACHI Kento, Masaya Denda and Akira Otaka :
IMPROVEMENT OF INSULIN SYNTHESIS BY COMBINATION OF O-ACYL ISOPEPTIDE METHOD AND ONE-POT/STEPWISE DISULFIDE BOND FORMATION USING S-PROTECTED CYSTEINE SULFOXIDE,
第60回ペプチド討論会, Nov. 2023. Mika Ohhira, OHKAWACHI Kento, Kaito Anzaki, Sayaka Tani, Mina Hojo, Masaya Denda, Hitoshi Mizuguchi and Akira Otaka :
DEVELOPMENT OF SYNTHETIC METHOD FOR DI-TYR CONTAINING PEPTIDES RELATED TO PARKINSONS DISEASE ENABLED BY OXIDATION SULFENYL TYR,
第60回ペプチド討論会, Nov. 2023. Daiki Sato, Chiho Shinozaki, Masaya Denda and Akira Otaka :
DEVELOPMENT OF INTERMOLECULAR ACYLATION PROTOCOL OF THREONINE BY A LATE-STAGE SEQUENTIAL ACYL TRANSFER DESULFURIZATION,
第60回ペプチド討論会, Nov. 2023. Daishiro Kobayashi, JUNYA Hayashi, Kohta Hidaka, OHKAWACHI Kento, Yutaka Kohmura, Masaya Denda and Akira Otaka :
TRYPTOPHAN-SELECTIVE PEPTIDE MODIFICATION USING S-ACETAMIDEMETHYL PROTECTED CYSTEINE SULFOXIDE UNDER MILD ACIDIC CONDITION AND ITS APPLICATION TO PEPTIDE HETERODIMERIZATION,
第60回ペプチド討論会, Nov. 2023. JUNYA Hayashi, Daishiro Kobayashi, Masaya Denda and Akira Otaka :
PREPARATION METHODOLOGY OF N-GLYOXYLYL PEPTIDE UTILIZING LOSSEN REARRANGEMENT,
第60回ペプチド討論会, Nov. 2023. 林隼矢, 小林大志朗, 傳田将也, 大髙章 :
Lossen転位を利用したペプチドN末端アルデヒド化法の開発と応用,
第49回反応と合成の進歩シンポジウム, 2023年11月. 小林大志朗, 林隼矢, 日高功太, 光村豊, 大川内健人, 傳田将也, 大髙章 :
Interrupted Pummerer反応によるTrp選択的修飾を利用したOne-potペプチドヘテロ二量化法の開発,
第49回反応と合成の進歩シンポジウム, 2023年11月. 太田りか, 左東大輝, 傳田将也, 大髙章 :
刺激応答性機能変換ペプチドの新規合成法の開発,
第62回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2023年10月. 江口亜希, 大川内健人, 大平実佳, 傳田将也, 大髙章 :
脂質ナノディスクを利用した難溶解性膜タンパク質化学合成法の開発,
第62回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2023年10月. 稲月勇斗, 辻貴志, 小林大志朗, 林隼矢, 傳田将也, 大髙章 :
Cysteinyl Prolyl Esterシステムを利用した新規医薬品放出制御システムの開発研究,
第62回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2023年10月. 永田綱基, 野中智貴, 小林大志朗, 傳田将也, 大髙章 :
Cys(MBzl)(O)を利用したTrp位置選択的脂肪鎖修飾法の開発と修飾GIP調製への応用,
第62回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2023年10月. 日高功太, 小林大志朗, 林隼矢, 大川内健人, 傳田将也, 大髙章 :
保護システインスルホキシドを用いたワンポット連続ジスルフィド形成によるインスリンの合成研究,
創薬懇話会2023 湯河原, 2023年6月. 左東大輝, 篠﨑千穂, 傳田将也, 大髙章 :
ユビキチン化の機能解明を志向した新規スレオニン側鎖アシル化法の開発,
日本ケミカルバイオロジー学会第17回年会, 2023年5月. 傳田将也, 野中智貴, 小林大志朗, 林隼矢, 安田拓真, 光村豊, 原田範雄, 稲垣暢也, 大髙章 :
S-保護システインスルホキシドを利用したトリプトファン選択的修飾法の開発,
日本ケミカルバイオロジー学会第17回年会, 2023年5月. 大川内健人, 安崎快登, 小林大志朗, 喜屋武龍二, 傳田将也, 重永章, 大髙章 :
S-保護システインスルホキシドを利用した残基選択的C-Hスルフェニル化反応の開発,
日本薬学会第143年会, 2023年3月. 左東大輝, 篠﨑千穂, 傳田将也, 大髙章 :
連続アシル転移を利用した分子内および分子間スレオニン側鎖アシル化法の開発,
日本薬学会第143年会, 2023年3月. 福原功起, 猪熊翼, 増井香奈, 傳田将也, 大髙章, 山田健一 :
N-2-Nitrophenylsulfenylイミノペプチドへのジアステレオ選択的インドリル化反応の開発,
日本薬学会第143年会, 2023年3月. 林隼矢, 小林大志朗, 傳田将也, 大髙章 :
アシルイミニウムカチオンを経由したペプチド主鎖修飾反応の開発,
第48回反応と合成の進歩シンポジウム, 2022年11月. 野中智貴, 小林大志朗, 倉岡瑛祐, 林隼矢, 安田拓真, 光村豊, 傳田将也, 原田範雄, 稲垣暢也, 大髙章 :
S-保護システインスルホキシドを利用したトリプトファン選択的脂肪鎖修飾法の開発と応用,
第39回メディシナルケミストリーシンポジウム, 2022年11月. 大平実佳, 大川内健人, 安崎快登, 北條三奈, 水口仁志, 傳田将也, 大髙章 :
スルフェニル化Tyrを利用したTyr-Tyrビアリール構造含有ペプチド合成法の開発,
第61回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2022年11月. 日高功太, 小林大志朗, 林隼矢, 大川内健人, 傳田将也, 大髙章 :
S-保護システインスルホキシドを利用したトリプトファン選択的修飾反応の開発とペプチドヘテロ二量化法への応用展開,
第61回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2022年11月. Tsubasa Inokuma, MASUI Kana, Masaya Denda, Akira Otaka and Ken-ichi Yamada :
Diastereoselective indolylation of N-2-nitrophenylsulfenyl iminopeptide for the synthesis of α-indolylglycine-containing peptide,
第59回ペプチド討論会, Oct. 2022. 日高功太, 小林大志朗, 林隼矢, 大川内健人, 傳田将也, 大髙章 :
DEVELOPMENT OF ONE-POT/STEPWISE DISULFIDE BOND-FORMING REACTION ENABLED BY S-PROTECTED CYSTEINE SULFOXIDE WITH ITS APPLICATION TO INSULIN SYNTHESIS,
第59回ペプチド討論会, 2022年10月. JUNYA Hayashi, Daishiro Kobayashi, Masaya Denda and Akira Otaka :
DEVELOPMENT OF INTRAMOLECULAR THIOETHERIFICATION ON PEPTIDE BACKBONE FOR CHEMICAL SYNTHESIS OF SACTIPEPTIDE,
第59回ペプチド討論会, Oct. 2022. 林隼矢, 小林大志朗, 傳田将也, 大髙章 :
ペプチド主鎖修飾反応の開発とチオエーテル含有環状ペプチド合成への展開,
第54回若手ペプチド夏の勉強会, 2022年8月. 小林大志朗, 林隼矢, 日高功太, 大川内健人, 光村豊, 傳田将也, 大髙章 :
保護システインスルホキシドを利用したペプチド・タンパク質Trp残基選択的修飾法の開発研究,
第54回若手ペプチド夏の勉強会, 2022年8月. 林隼矢, 小林大志朗, 傳田将也, 大髙章 :
Lossen転位を起点とした合成後期ペプチド主鎖ヘテロ化反応の開発,
創薬懇話会2022 in 名古屋, 2022年7月. 小林大志朗, 倉岡瑛祐, 光村豊, 林隼矢, 傳田将也, 大髙章 :
S-保護システインスルホキシドを利用したトリプトファン選択的修飾反応の開発研究,
日本薬学会第142年会, 2022年3月. 光村豊, 小林大志朗, 傳田将也, 大髙章 :
MBzl保護システインスルホキシドの芳香族化合物に対する反応性評価とペプチド架橋法への応用展開,
日本薬学会第142年会, 2022年3月. 左東大輝, 常松保乃加, 小西勇夢, 上田智子, 小宮千明, 傳田将也, 重永章, 大髙章 :
側鎖無保護ペプチドへの適用可能な合成後期ラクトン化法の開発,
日本薬学会第142年会, 2022年3月. 大西朗人, 東山晃子, 柳川瞬矢, 清良尚史, W John Regan, 大川内健人, 傳田将也, 福島圭穣, 大髙章, 藤野裕道 :
プロスタノイドEP4受容体の1アミノ酸変異によるシグナル伝達プロファイル変化,
第95回日本薬理学会年会，福岡, 2022年3月. 増井香奈, 榊原拓哉, 猪熊翼, 重永章, 大髙章, 山田健一 :
キラルN-Npsイミノペプチドへのインドールのジアステレオ選択的付加,
第60回日本薬学会中国四国支部学術大会, 2021年10月. 安崎快登, 大川内健人, 小林大志朗, 喜屋武龍二, 傳田将也, 重永章, 大髙章 :
RESIDUE-SPECIFIC MODIFICATION REACTION USING S-ACETAMIDOMETHYL CYSTEINE SULFOXIDE, Cys(Acm)(O),
第58回ペプチド討論会, 2021年10月. Daishiroh Kobayashi, Yutaka Kohmura, Junya Hayashi, Masaya Denda and Akira Otaka :
Development of copper and iron-mediated Cys-Trp-linking reaction,
第58回ペプチド討論会, Oct. 2021. 小林大志朗, 光村豊, 林隼矢, 傳田将也, 大髙章 :
銅添加を鍵としたシステイン-トリプトファン間架橋反応の開発研究,
第53回若手ペプチド夏の勉強会, 2021年8月. 野中智貴, 大川内健人, 傳田将也, 大髙章 :
Sulfanylmethyl DMAPを利用した環状ペプチド合成に関する研究,
第53回若手ペプチド夏の勉強会, 2021年8月. 安崎快登, 大川内健人, 小林大志朗, 喜屋武龍二, 傳田将也, 重永章, 大髙章 :
Acm 保護 Cys スルホキシドを利用した化学選択的 S-Aryl 化反応開発研究,
第53回若手ペプチド夏の勉強会, 2021年8月. 安崎快登, 大川内健人, 小林大志朗, 喜屋武龍二, 傳田将也, 重永章, 大髙章 :
保護Cysスルホキシドを利用したS–Aryl化環状ペプチド合成研究,
創薬懇話会2021 in 京都, 2021年6月. 光村豊, 小林大志朗, 杉木俊彦, 吉丸哲郎, 倉岡瑛祐, 傳田将也, 藤原敏道, 片桐豊雅, 大髙章 :
Cys-Trp 架橋型乳がん抑制ペプチド(ERAP)の合成及び活性評価,
創薬懇話会2021 in 京都, 2021年6月. 傳田将也, 小宮千明, 上田将弘, 月本準, 伊藤孝司, 重永章, 大髙章 :
既存モダリティの高度化を指向したペプチド・タンパク質新規修飾法の開発,
日本薬剤学会第36年会, 2021年5月. 有井紗由季, 上田将弘, 重永章, 大髙章, 猪熊翼, 山田健一, 石田竜弘, 奥平桂一郎 :
新規タンパク分解誘導剤によるチミジル酸合成酵素阻害メカニズムの解明,
日本薬剤学会第36年会, 2021年5月. 左東大輝, 常松保乃加, 上田智子, 小宮千明, 傳田将也, 重永章, 大髙章 :
側鎖無保護ペプチドを用いた環状デプシペプチド簡便合成法の開発,
日本薬学会第141年会, 2021年3月. 小林大志朗, 光村豊, 倉岡瑛祐, 傳田将也, 大髙章 :
S-保護システインスルホキシドを利用したCys-Trpチオエーテル結合形成反応の開発,
日本薬学会第141年会, 2021年3月. Daiki Satoh, Honoka Tsunematsu, Tomoko Ueda, Chiaki Komiya, Masaya Denda, Akira Shigenaga and Akira Otaka :
Development of a protection-free protocol for the synthesis of lactone peptides,
第57回ペプチド討論会, Nov. 2020. Daishiroh Kobayashi, Naoto Naruse, Masaya Denda, Akira Shigenaga and Akira Otaka :
Deprotection of S-acetamidomethyl cysteine mediated by copper salts,
第57回ペプチド討論会, Nov. 2020. Kento Ohkawachi, Daishiroh Kobayashi, Kyohei Morimoto, Akira Shigenaga, Masaya Denda, Kenzo Yamatsugu, Motomu Kanai and Akira Otaka :
A new thiol additive for one-pot sequential peptide ligation-desulfurization chemistry,
第57回ペプチド討論会, Nov. 2020. 猪熊翼, 増井香奈, 西田航大, 重永章, 大髙章, 山田健一 :
イミノペプチドへのインドール求核剤の不斉付加反応の開発,
第49回複素環化学討論会, 2020年9月. 金山忠史, 大川内健人, 清水太郎, 重永章, 大髙章, 石田竜弘, 奥平桂一郎 :
人工HDLの化学的性状と抗腫瘍効果への影響に関する検討,
日本薬学会第140年会, 2020年3月. 常松保乃加, 上田智子, 左東大輝, 小宮千明, 重永章, 大髙章 :
S-Oアシル転移を基盤とする環状デプシペプチドの合成,
日本薬学会第140年会, 2020年3月. 榊原拓哉, 猪熊翼, 増井香奈, 重永章, 大髙章, 山田健一 :
安定なα-イミノリン酸エステルの開発とキラルα-アミノリン酸の触媒的不斉合成への応用,
日本薬学会第140年会, 2020年3月. 安養寺啓太央, 粟飯原圭佑, 吉丸哲郎, 西川祐輔, 小松正人, 重永章, 片桐豊雅, 大髙章 :
乳がん細胞におけるBIG3-PHB2相互作用を標的とした高持続性架橋ペプチドの開発,
日本薬学会第140年会, 2020年3月. 杉山学, 大西朗人, 森崎巧也, 重永章, 福島圭穣, 大髙章, 藤野裕道 :
inteinシステムを用いたプロスタノイドEP4受容体の局在解析を目指して,
日本薬学会第140年会, 2020年3月. 大髙章 :
人工タンパク質創製のためのタンパク質チオエステル調製法の開発,
日本プロセス化学会2019ウィンターシンポジウム, 2019年12月. Tsubasa Inokuma, Kohdai Nishida, Kana Masui, Akira Shigenaga, Akira Otaka and Ken-ichi Yamada :
Chiral Phosphoric Acid-Catalyzed Asymmetric Mannich-Type Reaction Using Imino Peptide as Substrate,
第12回有機触媒シンポジウム, Dec. 2019. 種子島幸祐, 三井貴洋, 岩瀬璃奈, 成瀬公人, 重永章, 大髙章, 原孝彦 :
CpG DNAと CXCL14による自然免疫系の協調的な調節メカニズム,
第42回日本分子生物学会年会, 2019年12月. 中川美帆, 種子島幸祐, 三井貴洋, 成瀬公人, 重永章, 大髙章, 佐久間啓, 原孝彦 :
ケモカイン CXCL14の脳内ミクログリアに対する働き,
第42回日本分子生物学会年会, 2019年12月. 有井紗由季, 上田将弘, 重永章, 大髙章, 石田竜弘, 奥平桂一郎 :
プロテインノックダウン法を用いたチミジル酸合成酵素分解誘導剤開発,
第58回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2019年11月. 榊原拓哉, 猪熊翼, 増井香奈, 重永章, 大髙章, 山田健一 :
安定なα-イミノリン酸エステルへの触媒的不斉付加を用いるキラルα-アミノリン酸の合成,
第45回反応と合成の進歩シンポジウム, 2019年10月. 小林大志朗, 成瀬公人, 重永章, 大髙章 :
銅塩を利用するシステインS-保護基除去反応の開発,
第45回反応と合成の進歩シンポジウム, 2019年10月. Tsubasa Inokuma, Kana Masui, Kohdai Nishida, Akira Shigenaga, Akira Otaka and Ken-ichi Yamada :
Development of the direct asymmetric indolylation of imino peptide for synthesis of indolylglycine-containing peptide,
第56回ペプチド討論会, Oct. 2019. 小林大志朗, 西田航大, 猪熊翼, 重永章, 大髙章 :
Lossen rearrangement-mediated preparation of N-glyoxylyl peptide without addition of oxidant,
第56回ペプチド討論会, 2019年10月. 浜田麻衣, 中山淳, 中山慎一朗, 寺町順平, 辻大輔, 重永章, 安部正博, 伊藤孝司, 大髙章, 難波康祐 :
天然マクロライドの網羅的全合成が拓く新規多発性骨髄腫治療薬の開発研究,
2019年度第2回(第30回)日本プロセス化学会東四国フォーラムセミナー, 2019年10月. 大川内健人, 森本恭平, 成瀬公人, 山次健三, 重永章, 金井求, 大髙章 :
チオール導入型DMAP触媒を利用した環状ペプチド合成法の開発,
第51回若手ペプチド夏の勉強会, 2019年8月. 浜田麻衣, 森崎巧也, 中山淳, 寺町順平, 辻大輔, 重永章, 山本武範, 篠原康雄, 大髙章, 伊藤孝司, 安部正博, 難波康祐 :
天然マクロライドの全合成が拓く新規多発性骨髄腫治療薬,
創薬懇話会2019 in 秋保(仙台), 2019年6月. 小林大志朗, 成瀬公人, 重永章, 大髙章 :
銅塩を基点とする，タンパク合成を指向した反応開発研究,
創薬懇話会2019 in 秋保, 2019年6月. 安養寺啓太央, 粟飯原圭佑, 吉丸哲郎, 重永章, 片桐豊雅, 大髙章 :
がん抑制因子PHB2の部分配列を基盤とした乳がん阻害ペプチドの開発,
創薬懇話会2019 in 秋保, 2019年6月. 大髙章 :
天然に学ぶタンパク質化学とタンパク・ペプチド性医薬品の可能性,
神戸ポートアイランド創薬フォーラム, 2019年6月. 猪熊翼, 増井香奈, 西田航大, 重永章, 大髙章, 山田健一 :
ペプチドへの直接的不斉反応による異常アミノ酸含有ペプチド新規合成法の開発,
日本ケミカルバイオロジー学会第14回年会, 2019年6月. 金山忠史, 大川内健人, 清水太郎, 重永章, 大髙章, 石田竜弘, 奥平桂一郎 :
腫瘍DDSキャリアとしての人工HDLの調製および動態の評価,
日本薬剤学会第34年会, 2019年5月. 成瀬公人, 重永章, 大髙章 :
タンパク質合成を指向したチアゾリジン誘導体の脱保護法の開発,
日本薬学会第139年会, 2019年3月. 安養寺啓太央, 粟飯原圭佑, 吉丸哲郎, 重永章, 片桐豊雅, 大髙章 :
がん抑制タンパク質PHB2を基盤とした新規創薬シーズの開発,
日本薬学会第139年会, 2019年3月. 浜田麻衣, 中山淳, 重永章, 辻大輔, 寺町順平, 安部正博, 伊藤孝司, 大髙章, 難波康祐 :
新規Ynone化合物の創生・評価,
日本薬学会第139年会, 2019年3月. 猪熊翼, 西田航大, 重永章, 大髙章, 山田健一 :
ペプチドへの直接的不斉反応によるインドリルグリシン含有ペプチドの合成,
日本薬学会第139年会, 2019年3月. 三井貴洋, 種子島幸祐, 成瀬公人, 重永章, 大髙章, 原孝彦 :
CpG DNA/CXCL14複合体に対する候補受容体の発現クローニング,
第41回日本分子生物学会年会, 2018年11月. 岩瀬璃奈, 成瀬公人, 種子島幸祐, 重永章, 大髙章, 原孝彦 :
CXCL14とCpG DNAの相互作用によるTLR9活性化の特異性と責任領域の解析,
第41回日本分子生物学会年会, 2018年11月. 榊原拓哉, 猪熊翼, 重永章, 大髙章, 山田健一 :
非天然側鎖構造を有するα-アミノリン酸の実用的不斉合成,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 森崎巧也, 重永章, 大髙章 :
SECmideを基盤としたターンオン型蛍光クリーバブルリンカーの開発,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 上田将弘, 小宮千明, 重永章, 大髙章 :
酵素を利用したチオエステル化反応の効率化を指向したペプチドC末配列の修飾,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 金山忠史, 奥平桂一郎, 大川内健人, 清水太郎, 重永章, 大髙章, 石田竜弘 :
人工HDLの化学的性状と体内動態への影響に関する検討,
第57回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2018年11月. 猪熊翼, 岡田和貴, 西田航大, 重永章, 大髙章, 山田健一 :
ペプチドイミンに対する不斉1,2-付加を基盤とする非天然アミノ酸含有ペプチドの不斉合成,
第44回反応と合成の進歩シンポジウム, 2018年11月. 大髙章 :
自然に学ぶタンパク質化学,
ペプチド研究所フィッシャー祭, 2018年10月. 中西雅之, 古曳泰規, 重永章, 大髙章, 田中信忠, 北出幸夫, 日野真美, 野元裕 :
S-アデノシルホモシステイン加水分解酵素の蛍光性基質の開発,
第91回日本生化学会大会, 2018年9月. 上田将弘, 小宮千明, 重永章, 大髙章 :
酵素を利用したチオエステル調製のためのC末ペプチド配列の最適化,
第50回若手ペプチド夏の勉強会, 2018年8月. 安養寺啓太央, 粟飯原圭祐, 吉丸哲郎, 重永章, 片桐豊雅, 大髙章 :
がん抑制タンパク質PHB2からの創薬シード発掘,
第50回若手ペプチド夏の勉強会, 2018年8月. 河野誉良, 成瀬公人, 猪熊翼, 重永章, 大髙章 :
N-Sアシル基転移速度の向上を指向した新規補助基の開発,
第50回若手ペプチド夏の勉強会, 2018年8月. 大川内健人, 森本恭平, 成瀬公人, 重永章, 金井求, 大髙章 :
新規チオール触媒を利用した分子内ライゲーション法の開発,
第50回若手ペプチド夏の勉強会, 2018年8月. 森崎巧也, 中山淳, 難波康祐, 重永章, 大髙章 :
トレーサブルリンカーを用いた共有結合性低分子の標的同定,
第50回若手ペプチド夏の勉強会, 2018年8月. 成瀬公人, 大川内健人, 猪熊翼, 重永章, 大髙章 :
On-resinチオエステル化法から得られた知見とその応用,
第50回若手ペプチド夏の勉強会, 2018年8月. 小宮千明, 月本準, 上田将弘, 森崎巧也, 猪熊翼, 重永章, 伊藤孝司, 大髙章 :
加水分解酵素を利用したC末端特異的チオエステル化反応の開発,
第50回若手ペプチド夏の勉強会, 2018年8月. 榊原拓哉, 猪熊翼, 重永章, 大髙章, 山田健一 :
安定なイミンを用いたα-アミノリン酸の実用的不斉合成,
創薬懇話会 2018 in 志賀島, 2018年6月. 大川内健人, 成瀬公人, 重永章, 大髙章 :
新規チオール触媒を利用した環状ペプチド合成法の開発,
創薬懇話会 2018 in 志賀島, 2018年6月. 小宮千明, 月本準, 上田将弘, 森崎巧也, 猪熊翼, 重永章, 伊藤孝司, 大髙章 :
発現タンパク質に適用可能な新規チオエステル合成法の開発,
創薬懇話会 2018 in 志賀島, 2018年6月. 宮下直樹, 奥平桂一郎, 川原遥華, 津田雄介, 森本恭平, 辻耕平, 重永章, 大髙章, 石田竜弘 :
動脈硬化治療を指向した光制御型HDL構成ペプチドの開発,
日本薬剤学会第33年会, 2018年6月. 小宮千明, 月本準, 森崎巧也, 津田雄介, 宮島凜, 猪熊翼, 重永章, 伊藤孝司, 大髙章 :
均一修飾タンパク質の合成を指向したタンパク質C末端特異的活性化反応の開発,
日本薬学会第138年会, 2018年3月. 重永章, 大髙章 :
アシル基転移反応を基盤とする標的タンパク質精製・機能解明ツールの開発,
日本薬学会第138年会(シンポジウム中分子創薬研究のフロンティア), 2018年3月. 大髙章 :
タンパク質加水分解酵素を利用したタンパク質C末端特異的チオエステル化反応の開発,
ペプチド科学談話会2018, 2018年3月. 大髙章 :
脱不斉化ヘリックスペプチドはPPI 制御分子として機能するか?,
第1回徳島大学統合的がん創薬研究クラスター合同ミーティング, 2018年2月. 加藤有介, 古曳泰規, 西川祐輔, 佐川幾子, 傳田将也, 猪熊翼, 宍戸裕二, 重永章, 大髙章, 福井清 :
DAO分子表面に結合する阻害分子の計算科学的解析,
2017年度生命科学系学会合同年次大会, 2017年12月. 成瀬公人, 大川内健人, 猪熊翼, 重永章, 伊藤孝司, 大髙章 :
N-S-acyl-transfer-mediated On-resin Formation of Thioester with Practical Application to Peptide Synthesis,
第54回ペプチド討論会, 2017年11月. 小宮千明, 月本準, 森崎巧也, 津田雄介, 宮島凜, 猪熊翼, 重永章, 伊藤孝司, 大髙章 :
Development of methodology for producing thioesters from naturally occurring peptide sequence,
第54回ペプチド討論会, 2017年11月. 水口智晴, 伊藤恵理子, 中村光希, 扇田隆司, 馬場照彦, 重永章, 島内寿德, 奥平桂一郎, 大髙章, 斎藤博幸 :
脂質膜組成によるIowa変異型アポA-Iの線維化制御メカニズムの解明,
膜シンポジウム2017, 2017年11月. 大髙章 :
有機化学メジャーの薬剤師・創薬科学研究者を育成しよう,
第12回有機化学系教科担当教員会議, 2017年11月. 小宮千明, 津田雄介, 宮島凜, 猪熊翼, 重永章, 大髙章 :
タンパク質C末端特異的活性化反応の開発,
第35回メディシナルケミストリーシンポジウム, 2017年10月. 寺中孝久, 粟飯原圭佑, 山岡浩輔, 猪熊翼, 重永章, 大髙章 :
チオエステル等価体ユニットを利用した環状ペプチド効率的合成法の開発,
第35回メディシナルケミストリーシンポジウム, 2017年10月. 大髙章 :
モルフィネからはじまる薬の話,
第56回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会:高校生向けランチョンセミナー, 2017年10月. 芳野真奈, 宮本理人, 山岡朋美, 細井麻由, 森崎巧也, 安養寺啓太央, 重永章, 大髙章, 土屋浩一郎 :
骨格筋培養細胞でのレプチン作用におけるSIRT1の役割,
第56回中国四国支部学術大会, 2017年10月. 大川内健人, 成瀬公人, 重永章, 大髙章 :
On-resinチオエステル化を利用した環状ペプチド合成法の開発,
第56回日本薬学会・日本薬剤師会・日本大学病院薬剤師会中国四国支部学術大会, 2017年10月. 古曳泰規, 加藤有介, 西川祐輔, 頼田和子, 佐川幾子, 傳田将也, 猪熊翼, 重永章, 福井清, 大髙章 :
N-Sアシル基転移を基盤としたタンパク質ラベル化法を用いたD-アミノ酸酸化酵素阻害剤の結合サイト解明研究,
第56回日本薬学会・日本薬剤師会・日本大学病院薬剤師会中国四国支部学術大会, 2017年10月. 小久保友絵, 池田茉莉那, 渡部匡史, 重永章, 大髙章, 藤室雅弘 :
徳島大学化合物ライブラリーを用いた抗ヘルペスウイルス化合物の探索,
第67回日本薬学会近畿支部大会, 2017年10月. 大髙章 :
薬学基礎教育と臨床教育連携への提言-薬学における教養化学-,
第2回日本薬学教育学会大会, 2017年9月. 津田雄介, 猪熊翼, 重永章, 大髙章 :
タンパク質位置選択的修飾を目指したチオエステル調製法の開発,
第49回若手ペプチド夏の勉強会, 2017年8月. 西田航大, 猪熊翼, 重永章, 大髙章 :
ペプチドへの直接的不斉反応を基盤とする非天然アミノ酸含有ペプチドの新規効率的合成法の開発,
第49回若手ペプチド夏の勉強会, 2017年8月. 河野誉良, 成瀬公人, 猪熊翼, 重永章, 大髙章 :
N-Sアシル基転移反応の速度差を利用したライゲーション反応のための新規補助基の開発,
第49回若手ペプチド夏の勉強会, 2017年8月. 西田航大, 猪熊翼, 重永章, 大髙章 :
ペプチド創薬を指向した非天然アミノ酸含有ペプチドの新規効率的合成法の開発,
創薬懇話会2017 in 加賀, 2017年7月. 河野誉良, 成瀬公人, 猪熊翼, 重永章, 大髙章 :
タンパク質化学合成のための新規N-ペプチジルアニリド型補助基の開発,
創薬懇話会2017 in 加賀, 2017年7月. 川原遥華, 奥平桂一郎, 宮下直樹, 津田雄介, 森本恭平, 辻耕平, 重永章, 大髙章, 石田竜弘 :
光応答性アポリポタンパク質の開発,
日本薬剤学会第32年会, 2017年5月. 猪熊翼, 西田航大, 重永章, 大髙章 :
ペプチドへの直接的不斉反応を基盤とする新規非天然アミノ酸含有ペプチド合成テクノロジーの開発,
日本薬学会第137年会, 2017年3月. 灘井亮, 原矢佑樹, 西辻和親, 内村健治, 加藤くみ子, 重永章, 川上徹, 大髙章, 北條裕信, 坂下直実, 斎藤博幸 :
アルギニンペプチドのグリコサミノグリカン糖鎖を介した細胞膜透過機構に関する物理化学的解析,
日本薬学会第137年会, 2017年3月. 西田航大, 寺中孝久, 猪熊翼, 重永章, 大髙章 :
MnO2を用いたα-イミノカルボン酸誘導体の効率的合成法の開発,
日本薬学会第137年会, 2017年3月. 河野誉良, 成瀬公人, 猪熊翼, 重永章, 大髙章 :
チオエステル等価体として機能するタンパク質の化学合成のための新規補助基の開発,
日本薬学会第137年会, 2017年3月. 古曳泰規, 傳田将也, 藤川昴樹, 猪熊翼, 重永章, 小暮健太朗, 大髙章 :
N-Sulfanylethylanilideを用いた細胞内標的タンパク質ラベル化法の開発,
日本薬学会第137年会, 2017年3月. 森本恭平, 山次建三, 粟飯原圭佑, 猪熊翼, 重永章, 金井求, 大髙章 :
DMAP誘導体を用いた環状ペプチド合成法の開発,
日本薬学会第137年会, 2017年3月. 成瀬公人, 津田修吾, 大川内健人, 猪熊翼, 重永章, 大髙章 :
効率的タンパク質合成のためのSEAlideペプチドを用いたon-resinチオエステル化法の開発,
日本薬学会第137年会, 2017年3月. 種子島幸祐, 高橋伶奈, 塗谷秀子, 成瀬公人, 辻耕平, 重永章, 大髙章, 原孝彦 :
CXCケモカインCXCL14はCpG DNAに結合し，Toll-like receptor 9シグナルを活性化する,
第39回日本分子生物学会年会, 2016年12月. 津田雄介, 重永章, 辻耕平, 傳田将也, 佐藤浩平, 北風圭介, 中村太寛, 猪熊翼, 伊藤孝司, 大髙章 :
タンパク質位置選択的修飾を指向したチオエステル調製法の開発,
第34回メディシナルケミストリーシンポジウム, 2016年12月. 成瀬公人, 種子島幸祐, 辻耕平, 猪熊翼, 重永章, 原孝彦, 大髙章 :
N-Sulfanylethylanilideペプチドを利用したケモカイン誘導体の合成とToll-like receptor 9の活性化への影響について,
第34回メディシナルケミストリーシンポジウム, 2016年12月. 森崎巧也, 傳田将也, 辻大輔, 山本純, 猪熊翼, 伊藤孝司, 重永章, 大髙章 :
SEAlideを基盤とした標的タンパク質精製ツールの開発研究,
第34回メディシナルケミストリーシンポジウム, 2016年12月. 伊藤幸裕, 粟飯原圭佑, Paolo Mellini, 東條敏史, 太田庸介, 津元裕樹, Viswas Raja Solomon, Peng Zhan, 鈴木美紀, 小笠原大介, 重永章, 猪熊翼, 中川秀彦, 宮田直樹, 水上民夫, 大髙章, 鈴木孝禎 :
ヒドラジン構造を持つペプチド性LSD1阻害薬の創製,
第34回メディシナルケミストリーシンポジウム, 2016年12月. 水口智晴, 三河志穂, 馬場照彦, 島内寿徳, 重永章, 奥平桂一郎, 大髙章, 斎藤博幸 :
アミロイドーシス変異アポA-I Iowaの脂質膜結合状態の解析,
膜シンポジウム2016, 2016年12月. 成瀬公人, 江藤三弘, 猪熊翼, 重永章, 大髙章 :
N-Sulfanylethylcoumarinylamide (SECmide) を利用したN-Sアシル転移促進剤の探索とペプチド合成への応用,
第42回反応と合成の進歩シンポジウム, 2016年11月. 西田航大, 猪熊翼, 重永章, 大髙章 :
非天然アミノ酸含有ペプチドの新規効率的合成法の開発,
第55回日本薬学会・日本薬剤師会・日本大学病院薬剤師会中国四国支部学術大会, 2016年11月. 成瀬公人, 佐藤浩平, 中村太寛, 猪熊翼, 重永章, 大髙章 :
マンノース6リン酸修飾型GM2活性化タンパク質の合成研究,
第55回日本薬学会・日本薬剤師会・日本大学病院薬剤師会中国四国支部学術大会, 2016年11月. 粟飯原圭佑, 寺中孝久, 山岡浩輔, 猪熊翼, 重永章, 大髙章 :
ケミカルバイオロジー研究を指向した環状ペプチドtrichamideの合成研究,
第55回日本薬学会・日本薬剤師会・日本大学病院薬剤師会中国四国支部学術大会, 2016年11月. 佐藤智恵美, 阿部真治, 岡田直人, 石田竜弘, 土屋浩一郎, 大髙章, 川添和義 :
地域薬局における災害対策の現状と課題,
第55回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2016年11月. 灘井亮, 原矢佑樹, 西辻和親, 内村健治, 加藤くみ子, 重永章, 川上徹, 大髙章, 大髙章, 北條裕信, 坂下直実, 斎藤博幸 :
Sulfated glycosaminoglycans promote cell membrane penetration of arginine peptides via enthalpy-driven interactions,
第53回ペプチド討論会, 2016年10月. 三河志穂, 水口智晴, 森田いずみ, 大山浩之, 馬場照彦, 重永章, 島内寿徳, 小林典裕, 大髙章, 斎藤博幸 :
Effect of heparin on amyloid fibril formation of apoA-I fragment peptides,
第53回ペプチド討論会, 2016年10月. 伊藤幸裕, 粟飯原圭佑, Paolo Mellini, 東條敏史, 太田庸介, 津元裕樹, Viswas Raja Solomon, Peng Zhan, 鈴木美紀, 小笠原大介, 重永章, 猪熊翼, 中川秀彦, 宮田直樹, 水上民夫, 大髙章, 鈴木孝禎 :
Design, synthesis and biological evaluation of SNAIL1 peptide-based lysine specific demethylase 1 inhibitors,
第53回ペプチド討論会, 2016年10月. 山岡浩輔, 粟飯原圭佑, 成瀬公人, 猪熊翼, 重永章, 大髙章 :
One-pot sequential native chemical ligations using photocaged crypto-thioester,
第53回ペプチド討論会, 2016年10月. 森崎巧也, 傳田将也, 山本純, 辻大輔, 猪熊翼, 伊藤孝司, 重永章, 大髙章 :
Development of N-sulfanylethylanilide (SEAlide)-based traceable linker for enrichment and selective labeling of target proteins,
第53回ペプチド討論会, 2016年10月. 寺中孝久, 粟飯原圭佑, 山岡浩輔, 猪熊翼, 重永章, 大髙章 :
Synthetic study of trichamide using Cys-free ligation,
第53回ペプチド討論会, 2016年10月. 中村太寛, 重永章, 成瀬公人, 猪熊翼, 大髙章 :
Tailored Synthesis of 162-Residue S-Monoglycosylated GM2-Activator Protein (GM2AP) Analogues Applicable to the Preparation of a Protein Library,
第53回ペプチド討論会, 2016年10月. 粟飯原圭佑, 吉丸哲郎, 小松正人, 重永章, 片桐豊雅, 大髙章 :
Development of stapled peptides targeting BIG3-PHB2 interaction in breast cancer cells,
第53回ペプチド討論会, 2016年10月. 桑原智希, 水野彰, 福田隼, 渡邉瑞貴, 神田敦宏, 石田晋, 大髙章, 周東智 :
Design and synthesis of the spiro-cyclopropane scaffold peptidomimetics minicking both alpha-helix and beta-strand,
第53回ペプチド討論会, 2016年10月. 川添和義, 阿部真治, 清水太郎, 石田竜弘, 大髙章 :
徳島大学発「インタラクティブYAKUGAKUJIN」の育成―新しい視点に立脚した教育の開発と実践―,
第1回日本薬学教育学大会, 2016年8月. 水口智晴, 三河志穂, 馬場照彦, 島内寿徳, 重永章, 奥平桂一郎, 大髙章, 斎藤博幸 :
Iowa変異型アポA-Iによる脂質膜環境下でのアミロイド線維形成,
第4回日本アミロイド―シス研究会学術集会, 2016年8月. 寺中孝久, 粟飯原圭佑, 重永章, 猪熊翼, 大髙章 :
Cys-free ligationを用いた環状ペプチドTrichamideの合成研究,
第48回若手ペプチド夏の勉強会, 2016年8月. 成瀬公人, 佐藤浩平, 中村太寛, 猪熊翼, 重永章, 大髙章 :
リソソーム移行型GM2活性化タンパク質の合成研究,
第48回若手ペプチド夏の勉強会, 2016年8月. 松浦和則, 植村明仁, 稲葉央, 古曳泰規, 重永章, 大髙章 :
光誘起ペプチド繊維成長による走光性リポソームの創製,
第26回バイオ・高分子シンポジウム, 2016年7月. 山岡浩輔, 粟飯原圭佑, 成瀬公人, 猪熊翼, 重永章, 大髙章 :
光応答型チオエステル等価体を用いた多成分One-pot NCL法の開発研究,
創薬懇話会2016 in 蓼科, 2016年6月. 寺中孝久, 粟飯原圭佑, 重永章, 猪熊翼, 大髙章 :
中分子創薬を指向した環状ペプチドTrichamideの合成研究,
創薬懇話会2016 in 蓼科, 2016年6月. 頼田和子, 黒澤すみれ, 吉田結理, 大髙章, 柏田良樹, 佐野茂樹, 南川典昭, 福井清 :
ヒトD-アミノ酸酸化酵素のエフェクター探索と構造活性相関,
日本ビタミン学会第68回大会, 2016年6月. 古曳泰規, 傳田将也, 森崎巧也, 辻大輔, 猪熊翼, 伊藤孝司, 重永章, 大髙章 :
''SEAL-tag''を基盤とした細胞内での標的タンパク質ラベル化法の開発,
日本ケミカルバイオロジー学会第11回年会, 2016年6月. 森崎巧也, 傳田将也, 辻大輔, 山本純, 猪熊翼, 伊藤孝司, 重永章, 大髙章 :
標的タンパク質精製ツール"SEAlide-based traceable linker"の開発,
日本ケミカルバイオロジー学会第11回年会, 2016年6月. 松浦和則, 植村明仁, 中原正彦, 古谷昌大, 重永章, 小宮千明, 大髙章 :
光誘起ペプチドナノファイバー成長の時空間制御,
第65回高分子学会年次学会, 2016年5月. 灘井亮, 武知佑樹, 西辻和親, 内村健治, 加藤くみ子, 重永章, 川上徹, 大髙章, 北條裕信, 坂下直実, 斎藤博幸 :
アルギニンペプチドの細胞膜透過はグリコサミノグリカン糖鎖へのエンタルピー依存的結合によって促進される,
日本膜学会第38年会, 2016年5月. 川原遥華, 奥平桂一郎, 辻耕平, 津田雄介, 森本恭平, 木村仁, 假屋園大和, 大村理紗, 市野晨人, 杉原涼, 西辻和親, 重永章, 坂下直実, 大髙章, 斎藤博幸 :
光応答性アボ A-I 模倣ペプチドの開発研究,
日本薬学会第136年会, 2016年3月. 重永章, 大髙章 :
ペプチド化学を基盤としたケミカルバイオロジー研究のための基盤技術の開拓,
日本薬学会第136年会, 2016年3月. 寺中孝久, 粟飯原圭佑, 江藤三弘, 猪熊翼, 重永章, 大髙章 :
環状ペプチドTrichamideの合成研究,
日本薬学会第136年会, 2016年3月. 江藤三弘, 森本恭平, 辻耕平, 猪熊翼, 重永章, 大髙章 :
チオエステル等価体としてのN-sulfanylethylcoumarinylamide (SECmide) の開発及びペプチド合成への応用,
日本薬学会第136年会, 2016年3月. 森崎巧也, 傳田将也, 中村太寛, 辻大輔, 山本純, 猪熊翼, 伊藤孝司, 重永章, 大髙章 :
標的タンパク質の高効率的同定を可能とする新規リンカー分子の開発研究,
日本薬学会第136年会, 2016年3月. 成瀬公人, 佐藤浩平, 中村太寛, 猪熊翼, 重永章, 大髙章 :
マンノース六リン酸修飾型GM2活性化タンパク質の合成研究,
日本薬学会第136年会, 2016年3月. 山岡浩輔, 粟飯原圭佑, 成瀬公人, 猪熊翼, 重永章, 大髙章 :
光応答型チオエステル等価体を用いたOne-potタンパク質化学合成法の開発,
日本薬学会第136年会, 2016年3月. 高橋伶奈, 種子島幸祐, 辻耕平, 重永章, 大髙章, 原孝彦 :
ケモカインCXCL14は癌細胞のヘパラン硫酸に高親和性で結合する,
第38回日本分子生物学会年会・第88回日本生化学会大会合同大会, 2015年12月. 大髙章 :
創薬人育成教育から見えてきた薬学教育の将来について-薬の顔相学-,
第25回医療薬学会年会「教育セミナー」, 2015年11月. 小宮千明, 粟飯原圭佑, 猪熊翼, 重永章, 大髙章 :
Development of intein-inspired peptide bond processing device,
第52回ペプチド討論会, 2015年11月. 宮島凜, 津田雄介, 猪熊翼, 重永章, 大髙章 :
Preparation of peptide thioesters from naturally occuring sequences using a chemical protocol,
第52回ペプチド討論会, 2015年11月. 阿部真治, 佐藤智恵美, 山本香織, 東満美, 大髙章 :
薬学体験実習における屋根瓦方式導入の有用性,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会 (高知), 2015年11月. 松岡恒輝, 佐藤陽一, 大髙章, 山内あい子 :
薬物の胎児毒性に関する機械学習による予測と化学構造特性の解析,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年11月. 岡田直人, 阿部真治, 佐藤智恵美, 東満美, 川添和義, 大髙章, 石澤啓介 :
徳島大学病院における模擬体験型学習を用いた実務実習の評価,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年11月. 佐藤智恵美, 山本香織, 阿部真治, 岡田直人, 土屋浩一郎, 東満美, 大髙章 :
病院・薬局実務実習における実習生の主体性育成に向けての取組み:課題発見型レポートの効果の検証,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年11月. 森崎巧也, 傳田将也, 辻大輔, 山本純, 折原賢祐, 猪熊翼, 伊藤孝司, 宍戸宏造, 重永章, 大髙章 :
SEAlideを利用した標的タンパク質精製ツール ''トレーサブルリンカー''の開発研究,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年10月. 山岡浩輔, 粟飯原圭佑, 成瀬公人, 猪熊翼, 重永章, 大髙章 :
多成分縮合を可能とする光応答型チオエステル等価体の開発,
第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2015年10月. 猪熊翼, 岩本和也, 坂本健, 重永章, 大髙章 :
N-Sulfanylethylanilide (SEAlide)を基盤としたタンパク質-ペプチドコンジュゲーション法の開発,
第41回反応と合成の進歩シンポジウム, 2015年10月. 寺中孝久, 猪熊翼, 重永章, 大髙章 :
α-イミノカルボン酸誘導体の効率的合成法の開発と非天然α-アミノ酸合成への応用,
第41回反応と合成の進歩シンポジウム, 2015年10月. 重永章, 佐藤浩平, 猪熊翼, 大髙章 :
非天然型アミノ酸を含むタンパク質の調製を志向したタンパク質完全化学合成法の開拓,
第64回高分子討論会(特定テーマ融合マテリアルの精密構造制御と機能創製), 2015年9月. 寺中孝久, 粟飯原圭佑, 猪熊翼, 重永章, 大髙章 :
チアゾール含有環状ペプチドTrichamideの合成研究,
第三十一回若手化学者のための化学道場, 2015年8月. 小宮千明, 粟飯原圭佑, 猪熊翼, 重永章, 大髙章 :
タンパク質自己編集システムを範としたアミド結合切断反応の開発,
第三十一回若手化学者のための化学道場, 2015年8月. 森崎巧也, 傳田将也, 辻大輔, 山本純, 折原賢祐, 猪熊翼, 伊藤孝司, 宍戸宏造, 重永章, 大髙章 :
標的タンパク質の効率的精製および選択的ラベル化を可能とするケミカルツールの開発研究,
第三十一回若手化学者のための化学道場, 2015年8月. 山岡浩輔, 粟飯原圭佑, 成瀬公人, 猪熊翼, 重永章, 大髙章 :
光応答型チオエステル等価体を利用した多成分One-pot NCL法の開発,
第三十一回若手化学者のための化学道場, 2015年8月. 傳田将也, 森崎巧也, 猪熊翼, 佐藤陽一, 山内あい子, 重永章, 大髙章 :
N-Sアシル基転移反応を基盤としたin cellタンパク質ラベル化法の開発,
第47回若手ペプチド夏の勉強会, 2015年8月. 森崎巧也, 傳田将也, 辻大輔, 山本純, 折原賢裕, 猪熊翼, 伊藤孝司, 宍戸宏造, 重永章, 大髙章 :
標的タンパク質の高効率同定を可能とするケミカルツールの開発研究,
第47回若手ペプチド夏の勉強会, 2015年8月. 山岡浩輔, 粟飯原圭佑, 成瀬公人, 猪熊翼, 重永章, 大髙章 :
光応答性補助基を用いた4成分One-pot NCL法の開発,
第47回若手ペプチド夏の勉強会, 2015年8月. 傳田将也, 森崎巧也, 猪熊翼, 佐藤陽一, 山内あい子, 重永章, 大髙章 :
N-Sアシル基転移反応を利用した新規ラベル化試薬の開発,
創薬懇話会2015 in 徳島, 2015年7月. 津田雄介, 重永章, 辻耕平, 傳田将也, 佐藤浩平, 北風圭介, 中村太寛, 猪熊翼, 伊藤孝司, 大髙章 :
タンパク質半化学合成を指向した配列特異的チオエステル化法の開発,
創薬懇話会2015 in 徳島, 2015年7月. 大髙章, 佐藤浩平, 重永章 :
化学合成によるタンパク質製剤調製への挑戦,
第15回日本蛋白質科学会年会, 2015年6月. 中村太寛, 重永章, 佐藤浩平, 津田雄介, 猪熊翼, 大髙章 :
GM2活性化タンパク質誘導体の第二世代化学合成法の確立,
日本ケミカルバイオロジー学会第10回年会, 2015年6月. 三河志穂, 水口智晴, 辻耕平, 重永章, 島内寿徳, 大髙章, 斎藤博幸 :
アポA-Iアミロイド線維形成に与える脂質膜とヘパリンの影響,
日本膜学会第37年会, 2015年5月. 武知佑樹, 田中健斗, 辻耕平, 麻見安雄, 井澤浩則, 重永章, 大髙章, 川上亘作, 斎藤博幸 :
シクロデキストリン架橋型キトサン-pH応答性ペプチド複合体による細胞コレステロール排出促進作用,
日本膜学会第37年会, 2015年5月. 三河志穂, 水口智晴, 辻耕平, 馬場照彦, 重永章, 大髙章, 斎藤博幸 :
アルギニン変異apoA-Iフラグメントのアミロイド線維形成性,
日本薬学会第135年会, 2015年3月. 成瀬公人, 佐藤浩平, 坂本健, 猪熊翼, 重永章, 大髙章 :
M6P修飾型GM2APの合成検討,
日本薬学会第135年会, 2015年3月. 小倉圭司, 平川寛子, 森崎巧也, 山本純, 戎野紘司, 宮本理人, 石澤啓介, 土屋浩一郎, 重永章, 大髙章 :
低酸素環境応答型アミノ酸の開発研究,
日本薬学会第135年会, 2015年3月. 小宮千明, 粟飯原圭佑, 猪熊翼, 重永章, 大髙章 :
プロテインスプライシング模倣型ペプチド結合切断デバイスの開発研究,
日本薬学会第135年会, 2015年3月. 中村太寛, 重永章, 佐藤浩平, 津田雄介, 坂本健, 猪熊翼, 大髙章 :
GM2活性化タンパク質誘導体の第二世代化学合成法の開発研究,
日本薬学会第135年会, 2015年3月. 北未来, 佐藤浩平, 猪熊翼, 重永章, 大髙章 :
Protein trans-splicingの高速化を指向したN-intein合成法の開発研究,
日本薬学会第135年会, 2015年3月. 山本純, 森崎巧也, 北未来, 小宮千明, 重永章, 佐藤陽一, 山内あい子, 大髙章 :
標的タンパク質の効率的濃縮および選択的ラベル化を可能とするチオール応答型トレーサブルリンカーの開発,
第32回メディシナルケミストリーシンポジウム, 2014年11月. 戎野紘司, 傳田将也, 小倉圭司, 猪熊翼, 重永章, 大髙章 :
細胞内シグナル伝達機構解明を指向したケージド非水解性リン酸化アミノ酸の合成とその機能評価,
第40回反応と合成の進歩シンポジウム, 2014年11月. 粟飯原圭佑, 小宮千明, 重永章, 猪熊翼, 高橋大輔, 大髙章 :
固-液融合型ペプチド合成法を用いた架橋ペプチド効率的合成法の開発,
第40回反応と合成の進歩シンポジウム, 2014年11月. 小宮千明, 粟飯原圭佑, 猪熊翼, 重永章, 大髙章 :
タンパク質機能制御を指向したプロテインスプライシング模倣型アミド結合切断反応の開発,
第40回反応と合成の進歩シンポジウム, 2014年11月. 山岡朋美, 宮本理人, 川崎彩, 山根萌, 高橋梨恵, 石澤啓介, 宮島凛, 重永章, 大髙章, 土屋浩一郎 :
Leptinによる骨格筋培養細胞での代謝制御作用におけるSIRT1の役割,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 津田雄介, 重永章, 傳田将也, 佐藤浩平, 北風圭介, 中村太寛, 猪熊翼, 伊藤孝司, 大髙章 :
新規タンパク質チオエステル調製法の開発,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 中村太寛, 重永章, 佐藤浩平, 津田雄介, 坂本健, 猪熊翼, 大髙章 :
GM2活性化タンパク質アナログの第二世代化学合成法の開発研究,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 江藤三弘, 傳田将也, 佐藤浩平, 坂本健, 猪熊翼, 重永章, 大髙章 :
ペプチドチオエステル調製のためのクマリン型補助基の開発,
第53回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2014年11月. 假屋園大和, 新村航, 辻耕平, 重永章, 大髙章, 斎藤博幸 :
DESIGN OF NANODISC SCAFFOLD PEPTIDE (NSP),
第51回ペプチド討論会, 2014年10月. Yusuke Tsuda, Akira Shigenaga, Masaya Denda, Kohei Sato, Keisuke Kitakaze, Takahiro Nakamura, Tsubasa Inokuma, Kouji Itou and Akira Otaka :
Preparation of Peptide/protein Thioesters Using a Chemical Protocol Applicable to Expressed Proteins.,
51th The Japanese Peptide Society, Oct. 2014. Mitsuhiro Eto, Masaya Denda, Kohei Sato, Ken Sakamoto, Tsubasa Inokuma, Akira Shigenaga and Akira Otaka :
Preparation of peptide thioesters using N-sulfanylethylcoumarinylamide peptide,
第51回ペプチド討論会, Oct. 2014. Kohei Tsuji, Kohei Sato, Ken Sakamoto, Kosuke Tanegashima, Akira Shigenaga, Tsubasa Inokuma, Takahiko Hara and Akira Otaka :
One-pot chemical synthesis of CXCL14 using N-sulfanylethylanilide peptide,
第51回ペプチド討論会, Oct. 2014. Kohei Sato, Keisuke Kitakaze, Ken Sakamoto, Akira Shigenaga, Tsubasa Inokuma, Daisuke Tsuji, Kouji Itou and Akira Otaka :
Development of N-glycosylated asparagine ligation and its application to total chemical synthesis of GM2 activator protein,
51th The Japanese Peptide Society, Oct. 2014. 松浦和則, 古谷昌大, 植村明仁, 重永章, 小宮千明, 大髙章 :
光切断により誘起されるペプチドナノファイバー成長システムの創製,
第63回高分子討論会, 2014年9月. 大髙章 :
薬学教育の現状と期待(創薬研究から),
日本学術会議日本薬学会共催シンポジウム「薬学教育への期待:4年制薬学教育のあり方と参照基準の作成に向けて」, 2014年8月. 辻耕平, 重永章, 猪熊翼, 原孝彦, 大髙章 :
二量体化したCXCL14 C端側領域はCXCL12アンタゴニストとなる,
第46回若手ペプチド夏の勉強会, 2014年8月. 津田雄介, 重永章, 傳田将也, 佐藤浩平, 中村太寛, 猪熊翼, 大髙章 :
新規タンパク質チオエステル調製法 ''SQAT system'' の開発,
第46回若手ペプチド夏の勉強会, 2014年8月. 中村太寛, 重永章, 佐藤浩平, 津田雄介, 坂本健, 猪熊翼, 大髙章 :
第二世代hGM2AP完全化学合成法の開発研究,
第46回若手ペプチド夏の勉強会, 2014年8月. 江藤三弘, 傳田将也, 佐藤浩平, 坂本健, 猪熊翼, 重永章, 大髙章 :
N-Sulfanylethylcoumarinylamide (SECmide) を用いたペプチドチオエステル調製法の開発,
第46回若手ペプチド夏の勉強会, 2014年8月. 小宮千明, 粟飯原圭佑, 猪熊翼, 重永章, 大髙章 :
アスパラギン誘導体を用いたインテイン模倣型ペプチド結合切断システムの開発,
第46回若手ペプチド夏の勉強会, 2014年8月. 宮島凜, 津田雄介, 佐藤浩平, 猪熊翼, 重永章, 大髙章 :
天然型アミノ酸配列からのチオエステル合成,
第46回若手ペプチド夏の勉強会, 2014年8月. 森崎巧也, 山本純, 重永章, 猪熊翼, 大髙章 :
SEAlideを基盤としたトレーサブルリンカーの開発研究,
第46回若手ペプチド夏の勉強会, 2014年8月. 粟飯原圭佑, 小宮千明, 重永章, 猪熊翼, 高橋大輔, 大髙章 :
オレフィンメタセシスを用いた架橋ペプチド効率的合成法の開発,
創薬懇話会2014, 2014年7月. 津田雄介, 重永章, 佐藤浩平, 中村太寛, 北風圭介, 猪熊翼, 伊藤孝司, 大髙章 :
天然アミノ酸配列に適用可能な新規タンパク質チオエステル合成法の開発,
日本ケミカルバイオロジー学会第9回年会, 2014年6月. 北未来, 山本純, 戎野紘司, 小宮千明, 宮本理人, 土屋浩一郎, 重永章, 大髙章 :
過酸化水素応答型ペプチド結合切断デバイスの開発研究,
日本ケミカルバイオロジー学会第9回年会, 2014年6月. 森口正登, 古谷昌大, 重永章, 小宮千明, 大髙章, 松浦和則 :
光切断によりβ-シート繊維成長するアニオン性ペプチドの分子設計,
第63回高分子学会年次大会, 2014年5月. 足立愛美, 辻耕平, 川島浩之, 重永章, 長尾耕治郎, 赤路健一, 大髙章, 斎藤博幸 :
フラグメントペプチドを用いたアポA-Iアミロイド線維形成領域の同定,
日本薬学会第134年会, 2014年3月. 辻耕平, 佐藤浩平, 坂本健, 種子島幸祐, 重永章, 原孝彦, 大髙章 :
SEAlideペプチドを用いたCXCL14のone-pot化学合成法の開発,
日本薬学会第134年会, 2014年3月. 大髙章, 重永章 :
インテインに学ぶ標的タンパク質研究手法の開発,
日本薬学会第134年会, 2014年3月. 佐藤浩平, 北風圭介, 坂本健, 重永章, 辻大輔, 伊藤孝司, 大髙章 :
GM2活性化タンパク質の収束的合成研究,
日本薬学会第134年会, 2014年3月. 傳田将也, 山本純, 佐藤浩平, 坂本健, 重永章, 佐藤陽一, 山内あい子, 大髙章 :
ラベル化試薬"SEAL-tag"の開発とCOX-1およびhCA1のラベル化,
日本薬学会第134年会, 2014年3月. 津田雄介, 重永章, 佐藤浩平, 中村太寛, 北風圭介, 猪熊翼, 伊藤孝司, 大髙章 :
発現タンパク質に適用可能な新規タンパク質チオエステル合成法の開発,
日本薬学会第134年会, 2014年3月. 江藤三弘, 傳田将也, 佐藤浩平, 坂本健, 猪熊翼, 重永章, 大髙章 :
N-Sulfanylethylcoumarinylamide (SECmide) を用いたペプチドチオエステル調製法の開発,
日本薬学会第134年会, 2014年3月. 小宮千明, 山本純, 猪熊翼, 重永章, 大髙章 :
還元的N-N結合切断反応の改良を基盤とした刺激応答型アミノ酸の実用的合成法の検討,
日本薬学会第134年会, 2014年3月. 宮島凜, 津田雄介, 佐藤浩平, 猪熊翼, 重永章, 大髙章 :
天然アミノ酸配列に適用可能な新規ペプチドチオエステル合成法の開発,
日本薬学会第134年会, 2014年3月. 森崎巧也, 山本純, 重永章, 佐藤陽一, 猪熊翼, 山内あい子, 大髙章 :
標的タンパク質の効率的濃縮および選択的ラベル化を可能とする新規リンカー分子の開発,
日本薬学会第134年会, 2014年3月. 古谷昌大, 松浦和則, 重永章, 小宮千明, 大髙章 :
光切断によりナノファイバー成長誘起されるペプチド分子システムの創製,
日本化学会第94春季年会, 2014年3月. 佐藤浩平, 傳田将也, 山本純, 坂本健, 重永章, 佐藤陽一, 山内あい子, 大髙章 :
タンパク質機能解明を指向した新規ラベル化試薬''SEAL-tag''の開発研究,
第31回メディシナルケミストリーシンポジウム, 2013年11月. 粟飯原圭佑, 重永章, 大髙章 :
オレフィンメタセシスを用いたGlu-Lys架橋ペプチド新規合成法の開発研究,
第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月. 戎野紘司, 傳田将也, 小倉圭司, 重永章, 大髙章 :
ケージド非水解性リン酸化アミノ酸含有ペプチドの合成法の確立と14-3-3βタンパク質への結合能の評価,
第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月. 小宮千明, 山本純, 重永章, 大髙章 :
刺激応答型アミノ酸の実用的合成法の開発検討,
第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月. 清水達彦, 宮島凜, 坂本健, 重永章, 大髙章 :
SEAlide peptideを用いた簡便なペプチドチオカルボン酸合成法の開発,
第52回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2013年10月. 山本純, 北未来, 重永章, 佐藤陽一, 山内あい子, 大髙章 :
標的タンパク質精製・選択的ラベル化ツール''Traceable Linker''の開発研究,
生命分子機能研究会2013学術集会, 2013年9月. 佐藤浩平, 北風圭介, 坂本健, 重永章, 辻大輔, 伊藤孝司, 大髙章 :
リソソーム病治療を指向したGM2活性化タンパク質アナログの完全化学合成,
生命分子機能研究会2013学術集会, 2013年9月. 大髙章 :
自然に学ぶペプチド化学,
第45回若手ペプチド夏の勉強会, 2013年7月. 山本純, 北未来, 重永章, 佐藤陽一, 山内あい子, 大髙章 :
標的タンパク質を釣り上げろ!∼トレーサブルリンカーの開発∼,
第45回若手ペプチド夏の勉強会, 2013年7月. 粟飯原圭佑, 重永章, 大髙章 :
オレフィンメタセシスを用いたLys-Glu架橋ペプチド新規合成法の開発研究,
第45回若手ペプチド夏の勉強会, 2013年7月. 坂本健, 佐藤浩平, 重永章, 辻大輔, 伊藤孝司, 大髙章 :
SEAlideユニットの効率的合成法の開発とその応用,
第45回若手ペプチド夏の勉強会, 2013年7月. 北未来, 山本純, 戎野紘司, 小宮千明, 重永章, 大髙章 :
過酸化水素応答型ペプチド結合切断能を有するアミノ酸の開発,
第45回若手ペプチド夏の勉強会, 2013年7月. 中村太寛, 津田雄介, 佐藤浩平, 坂本健, 重永章, 大髙章 :
NCL法におけるプロリルチオエステルの有用性の検討,
第45回若手ペプチド夏の勉強会, 2013年7月. 大髙章 :
ペプチド・タンパク質を基盤とする創薬展開への化学基盤の開拓,
創薬懇話会2013, 2013年7月. 戎野紘司, 傳田将也, 小倉圭司, 重永章, 大髙章 :
ケージド非水解性リン酸化アミノ酸含有ペプチドの合成と14-3-3βタンパク質への結合能評価,
日本ケミカルバイオロジー学会第8回年会, 2013年6月. 大髙章 :
標的タンパク質同定に向けたトレーサブルリンカーの開発,
新学術領域研究「天然物ケミカルバイオロジー∼分子標的と活性制御∼」第4回公開シンポジウム, 2013年5月. 山本純, 北未来, 重永章, 佐藤陽一, 山内あい子, 大髙章 :
標的タンパク質の精製・選択的ラベル化ツール「トレーサブルリンカー」の開発,
日本薬学会第133回年会, 2013年3月. 北未来, 山本純, 戎野紘司, 重永章, 大髙章 :
過酸化水素応答型アミノ酸の開発研究,
日本薬学会第133回年会, 2013年3月. 折原賢祐, 小林久剛, 兼松誠, 吉田昌裕, 中村崇洋, 辻大輔, 伊藤孝司, 重永章, 大髙章, 宍戸宏造 :
Aspergillide Cの活性評価および標的タンパクの探索,
日本薬学会第133年会, 2013年3月. 山本純, 傳田将也, 戎野紘司, 重永章, 佐藤陽一, 山内あい子, 大髙章 :
フッ化物イオン応答型トレーサブルリンカーを利用したタンパク質精製実験,
第30回メディシナルケミストリーシンポジウム, 2012年11月. 辻耕平, 種子島幸祐, 重永章, 粟飯原圭佑, 丁昊, 傳田将也, 原孝彦, 大髙章 :
CXCL14受容体の同定とそのアンタゴニストペプチドの合成,
第30回メディシナルケミストリーシンポジウム, 2012年11月. 佐藤浩平, 北風圭介, 坂本健, 重永章, 辻大輔, 伊藤孝司, 大髙章 :
リソソーム病治療薬を指向したヒトGM2活性化タンパク質誘導体の化学合成と活性評価,
第30回メディシナルケミストリーシンポジウム, 2012年11月. 戎野紘司, 傳田将也, 小倉圭司, 寺脇拓, 重永章, 大髙章 :
ケージド非水解性リン酸化アミノ酸含有ペプチドの合成とタンパク質結合能の評価,
第30回メディシナルケミストリーシンポジウム, 2012年11月. 傳田将也, 山本純, 坂本健, 重永章, 佐藤陽一, 山内あい子, 大髙章 :
タンパク質選択的ラベル化法の開発研究,
第51回日本薬学会・日本薬剤師会,日本病院薬剤師会中国四国支部学術大会, 2012年11月. 北未来, 山本純, 戎野紘司, 重永章, 大髙章 :
酸化ストレス応答型アミノ酸の開発研究,
第51回日本薬学会・日本薬剤師会,日本病院薬剤師会中国四国支部学術大会, 2012年11月. Akira Shigenaga, Keiji Ogura, Hiroko Hirakawa, Jun Yamamoto, Koji Ebisuno, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Akira Otaka :
Design and synthesis of hypoxia-responsive amino acid which causes peptide bond cleavage in hypoxic cells,
第49回ペプチド討論会, Nov. 2012. Ken Sakamoto, Kohei Sato, Akira Shigenaga, Kohei Tsuji, Shugo Tsuda, Hajime Hibino, Yuji Nishiuchi and Akira Otaka :
Development of efficient synthetic protocol for Fmoc amino acid-incorporated N-sulfanylethyl-aniline linker as peptide thioester precursor,
第49回ペプチド討論会, Nov. 2012. Kohei Sato, Keisuke Kitakaze, Ken Sakamoto, Akira Shigenaga, Daisuke Tsuji, Kouji Itou and Akira Otaka :
Convergent chemical synthesis of human GM2 activator protein analog using SEAlide chemistry,
第49回ペプチド討論会, Nov. 2012. Kohei Tsuji, Kosuke Tanegashima, Akira Shigenaga, Keisuke Aihara, Masaya Denda, Hao Ding, Takahiko Hara and Akira Otaka :
Synthesis of antagonistic peptide for putative CXCL14 receptor proteins and their identification,
第49回ペプチド討論会, Nov. 2012. 重永章, 大髙章 :
''化学''でペプチド・タンパク質をあやつる,
第28回若手化学者のための化学道場, 2012年9月. 大髙章 :
情報発信型人工タンパク質創製に向けた有機・生物有機化学的挑戦,
アステラス製薬シンポジウム, 2012年8月. 丁昊, 佐藤浩平, 森下巧, 重永章, 大髙章 :
4-チオプロリンを用いたDual-kinetic NCL法の開発,
第44回若手ペプチド夏の勉強会, 2012年8月. 佐藤浩平, 北風圭介, 坂本健, 重永章, 辻大輔, 伊藤孝司, 大髙章 :
タンパク質完全化学合成∼ケミストによるタンパク質医薬品開発を目指して∼,
第44回若手ペプチド夏の勉強会, 2012年8月. 傳田将也, 山本純, 佐藤浩平, 坂本健, 重永章, 佐藤陽一, 吉村好之, 山内あい子, 大髙章 :
新規タンパク質選択的ラベル化試薬''SEAL-tag''の開発研究,
日本ケミカルバイオロジー学会第7回年会, 2012年6月. 山本純, 傳田将也, 戎野紘司, 重永章, 佐藤陽一, 山内あい子, 大髙章 :
フッ化物イオン応答型トレーサブルリンカーを利用したタンパク質精製法の開発,
日本ケミカルバイオロジー学会第7回年会, 2012年6月. 大髙章 :
情報発信型人工タンパク質創製に向けた有機・生物有機化学的挑戦,
第101回有機合成シンポジウム2012年【春】, 2012年6月. 坂本健, 佐藤浩平, 津田修吾, 重永章, 大髙章 :
タンパク質化学合成を指向したN-アミノアシルN-置換アニリンリンカーの効率的合成法の開発,
日本薬学会第132回年会, 2012年3月. 戎野紘司, 山本純, 重永章, 大髙章 :
新規チオール応答型アミノ酸の合成とDNA放出システムへの展開,
日本薬学会第132回年会, 2012年3月. 粟飯原圭佑, 辻耕平, 丁昊, 傳田将也, 種子島幸祐, 重永章, 原孝彦, 大髙章 :
CXCL14・CXCL12デュアルアンタゴニストペプチドの創製,
日本薬学会第132回年会, 2012年3月. 傳田将也, 小倉圭司, 戎野紘司, 重永章, 大髙章 :
リン酸化タンパク質の機能解明に向けたケージド非水解性リン酸化アミノ酸含有ペプチドの合成研究,
日本薬学会第132回年会, 2012年3月. 丁昊, 佐藤浩平, 森下巧, 重永章, 大髙章 :
4-チオプロリンを用いたNative Chemical Ligation法の開発,
日本薬学会第132回年会, 2012年3月. 山本純, 田中智博, 傳田将也, 戎野紘司, 野村渉, 重永章, 玉村啓和, 大髙章 :
フッ化物イオン応答型アミノ酸の開発と標的タンパク質精製ツールへの応用,
日本薬学会第132回年会, 2012年3月. 大髙章 :
標的タンパク質捕捉の科学,
徳島大学大学院ヘルスバイオサイエンス研究部第8回公開シンポジウム, 2011年11月. 小倉圭司, 平川寛子, 傳田将也, 重永章, 大髙章 :
AMP化タンパク質の機能解明を指向したペプチド性分子ツールの開発,
第50回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2011年11月. 辻耕平, 住川栄健, 種子島幸祐, 重永章, 原孝彦, 大髙章 :
CXCL14およびその誘導体の効率的合成法の開発と活性評価,
第50回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2011年11月. 傳田将也, 小倉圭司, 戎野紘司, 重永章, 大髙章 :
リン酸化タンパク質の機能解明に向けた紫外線応答型リン酸化アミノ酸誘導体の合成研究,
第50回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2011年11月. 坂本健, 佐藤浩平, 津田修吾, 重永章, 大髙章 :
ペプチドチオエステル合成用アニリン型補助基への効率的アミノ酸導入法の開発,
第50回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会, 2011年11月. 小倉圭司, 平川寛子, 重永章, 大髙章 :
タンパク質AMP化の生理学的意義解明を指向した新規分子ツールの開発,
第37回反応と合成の進歩シンポジウム, 2011年11月. 丁昊, 佐藤浩平, 森下巧, 重永章, 大髙章 :
4-メルカプトプロリンを用いたペプチドフラグメント縮合法の開発,
第37回反応と合成の進歩シンポジウム, 2011年11月. 佐藤浩平, 津田修吾, 坂本健, 重永章, 大髙章 :
タンパク質化学合成を指向したワンポット4成分連続縮合法の開発,
第37回反応と合成の進歩シンポジウム, 2011年11月. Hao Ding, Kohei Sato, Ko Morishita, Akira Shigenaga and Akira Otaka :
Double-kinetically controlled proline ligation,
第48回ペプチド討論会, Sep. 2011. Akira Shigenaga, Hiroko Hirakawa, Jun Yamamoto, Keiji Ogura, Masaya Denda, Keiko Yamaguchi and Akira Otaka :
Caged ceramide which releases parent ceramide after UV-induced amide bond cleavage followed by intramolecular O-N acyl transfer,
第48回ペプチド討論会, Sep. 2011. Kohei Sato, Shugo Tsuda, Ken Sakamoto, Akira Shigenaga and Akira Otaka :
N-Sulfanylethylanilide peptide: a peptide thioester equivalent which can directly participate in native chemical ligation,
第48回ペプチド討論会, Sep. 2011. Akira Otaka and Akira Shigenaga :
Development of nucleocytoplasmic shuttle peptide using stimulus-responsive processing device,
日本生物物理学会第49回年会, Sep. 2011. 佐藤浩平, 津田修吾, 坂本健, 重永章, 大髙章 :
簡便かつ効率的タンパク質化学合成法の開発,
創薬懇話会2011, 2011年7月. 小倉圭司, 平川寛子, 重永章, 大髙章 :
タンパク質AMP化の生理学的意義解明に向けたAMP化アミノ酸誘導体の創製,
創薬懇話会2011, 2011年7月. 小倉圭司, 平川寛子, 重永章, 大髙章 :
AMP化タンパク質の機能解明に向けたAMP化アミノ酸誘導体の創製,
日本ケミカルバイオロジー学会第6回年会, 2011年5月. 辻大輔, 難波建多郎, 浦上裕行, 辻耕平, 重永章, 大髙章, 柏田良樹, 高石喜久, 伊藤孝司 :
ヒトiPS細胞に対する神経分化誘導能を持つ新規化合物の探索,
日本薬学会第131年会, 2011年3月. 重永章, 山本純, 西岡直美, 小倉圭司, 傳田将也, 大髙章 :
プロリン型触媒を用いた刺激応答型アミノ酸の不斉合成,
日本薬学会年会, 2011年3月. 山本純, 前田奈美, 田中智博, 傳田将也, 重永章, 野村渉, 玉村啓和, 大髙章 :
標的タンパク質の効率的濃縮と同定を指向したトレーサブルリンカーの開発,
日本薬学会年会, 2011年3月. 辻耕平, 住川栄健, 種子島幸祐, 重永章, 原孝彦, 大髙章 :
CXCL14およびその誘導体の多様性指向型化学合成とその活性評価,
日本薬学会年会, 2011年3月. 佐藤浩平, 津田修吾, 住川栄健, 辻耕平, 傳田将也, 坂本健, 重永章, 大髙章 :
クリプトチオエステル:ネイティブケミカルライゲーションに直接適用可能なペプチドチオエステル等価体,
日本薬学会年会, 2011年3月. 辻大輔, 難波建多郎, 浦上裕行, 重永章, 大髙章, 柏田良樹, 高石喜久, 伊藤孝司 :
未分化細胞に対する神経分化誘導作用を持つ化合物の探索と構造活性相関,
BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会合同大会), 2010年12月. 小倉圭司, 平川寛子, 重永章, 大髙章 :
AMP化タンパク質の機能解明に向けたフォスファターゼ抵抗性AMP化アミノ酸の創製,
第29回メディシナルケミストリーシンポジウム, 2010年11月. 山本純, 傳田将也, 前田奈美, 重永章, 大髙章 :
標的タンパク質の効率的濃縮と同定を指向したCleavable Linkerの創製,
第29回メディシナルケミストリーシンポジウム, 2010年11月. 辻耕平, 住川栄健, 種子島幸祐, 重永章, 原孝彦, 大髙章 :
ライブラリ構築を志向したCXCL14およびその誘導体の合成と活性評価,
創薬懇話会2010, 2010年11月. 森下巧, 山口圭子, 丁昊, 重永章, 赤路健一, 大髙章 :
システインプロテアーゼの活性調節を指向した機能性分子の開発,
第49回日本薬学会病院薬剤師会中国四国支部学術大会, 2010年11月. 山本純, 傳田将也, 前田奈美, 重永章, 大髙章 :
標的タンパク質の効率的濃縮と同定を指向したCleavable Linkerの開発,
第49回日本薬学会病院薬剤師会中国四国支部学術大会, 2010年11月. 辻耕平, 八巻陽子, 山本純, 重永章, 下東康幸, 大髙章 :
Synthesis of fluoroalkene dipeptide isosteres (FADIs) using intramolecular redox reaction with their incorporation into biologically active peptide,
第38回構造活性相関シンポジウム, 2010年10月. 山本純, 前田奈美, 重永章, 大髙章 :
ターゲットタンパク質の効率的濃縮と同定を指向したCleavable Linkerの開発,
日本ケミカルバイオロジー学会第5回年会, 2010年5月. 重永章, 大髙章 :
刺激応答型ペプチド結合切断反応を基盤としたペプチド機能制御,
日本薬学会年会, 2010年3月. 辻耕平, 山本純, 八巻陽子, 重永章, 大髙章 :
分子内Redox反応を利用したフルオロアルケンジペプチドイソスターの合成とそのα-アルキル化の検討,
日本薬学会年会, 2010年3月. 佐藤浩平, 津田修吾, 前田奈美, 重永章, 大髙章 :
N-置換アニリン型補助基の生理活性ペプチド合成への展開,
日本薬学会年会, 2010年3月. 小倉圭司, 平川寛子, 重永章, 大髙章 :
AMP化タンパク質の機能解明に向けた非水解性AMP化アミノ酸の創製,
日本薬学会年会, 2010年3月. 山本純, 住川栄健, 重永章, 古田寿昭, 大髙章 :
近赤外二光子励起応答型ペプチドの開発およびその光反応性の測定,
日本薬学会年会, 2010年3月. 森下巧, 山口圭子, 重永章, 赤路健一, 大髙章 :
チオールプロテアーゼの機能制御を指向した機能性分子の開発,
日本薬学会年会, 2010年3月. 山本純, 八巻陽子, 辻耕平, 重永章, 大髙章 :
分子内Redox反応を利用したフルオロアルケンジペプチドイソスターの合成とクライゼン型転位によるα-アリル化の検討,
創薬懇話会2009, 2009年12月. 森下巧, 山口圭子, 重永章, 大髙章 :
チオールプロテアーゼの活性制御を指向した刺激応答型チオール放出システムの開発,
第28回メディシナルケミストリーシンポジウム, 2009年11月. 住川栄健, 津田修吾, 重永章, 大髙章 :
ペプチドチオカルボン酸の効率的合成と新規ペプチドフラグメント縮合法への適用,
第35回反応と合成の進歩シンポジウム, 2009年11月. Akira Shigenaga, Yukiko Nishiyama, Nami Maeda and Akira Otaka :
Synthesis of cyclic peptides via on resin-intramolecular native chemical ligation followed by reductive release from resin,
第46回ペプチド討論会, Nov. 2009. 住川栄健, 津田修吾, 重永章, 大髙章 :
ペプチドチオカルボン酸の効率的合成とsequential NCL法への適用,
ケミカルバイオロジー学会第4回年会, 2009年5月. 平川寛子, 西岡直美, 山口圭子, 重永章, 大髙章 :
光刺激応答型アミド結合切断デバイスのケージドセラミド創製への応用,
ケミカルバイオロジー学会第4回年会, 2009年5月. 重永章, 津田修吾, 住川栄健, 大髙章 :
N-置換アニリン型補助基を用いたペプチドチオエステル合成法の開発,
ケミカルバイオロジー学会第4回年会, 2009年5月. 重永章, 山本純, 平川寛子, 山口圭子, 大髙章 :
任意の刺激応答型ペプチド結合切断デバイスの反応速度に与えるアミノ酸配列の影響,
日本薬学会年会, 2009年3月. 前田奈美, 津田修吾, 石澤祥衣, 重永章, 大髙章 :
分子内NCLを利用した環状ペプチド合成法の開発(1),
日本薬学会年会, 2009年3月. 西山由希子, 中本亜樹, 重永章, 大髙章 :
分子内NCLを利用した環状ペプチド合成法の開発(2),
日本薬学会年会, 2009年3月. 平川寛子, 西岡直美, 山口圭子, 重永章, 大髙章 :
光刺激応答型アミド結合切断反応のケージドセラミド創製への応用,
日本薬学会年会, 2009年3月. 住川栄健, 津田修吾, 重永章, 大髙章 :
蛋白質化学合成を指向した無保護ペプチドフラグメント順次縮合法の開発,
日本薬学会年会, 2009年3月. 平川寛子, 西岡直美, 山口圭子, 重永章, 大髙章 :
刺激応答型アミド結合切断デバイスを利用したケージドセラミドの創製,
創薬懇話会2008, 2008年12月. 山本純, 住川栄健, 西岡直美, 重永章, 古田寿昭, 大髙章 :
近赤外二光子励起応答型ペプチド結合切断デバイスの開発,
第47回日本薬学会病院薬剤師会中国四国支部学術大会, 2008年11月. 森下巧, 津田修吾, 前田奈美, 重永章, 大髙章 :
ペプチド結合切断能を有する側鎖修飾型アスパラギンの開発,
第47回日本薬学会病院薬剤師会中国四国支部学術大会, 2008年11月. 前田奈美, 津田修吾, 重永章, 大髙章 :
N-Sアシルシフトを利用した環状ペプチドライブラリー構築の試み,
第47回日本薬学会病院薬剤師会中国四国支部学術大会, 2008年11月. 平川寛子, 西岡直美, 山口圭子, 重永章, 大髙章 :
光刺激応答型アミド結合切断反応を利用したケージドセラミドの創製,
第47回日本薬学会病院薬剤師会中国四国支部学術大会, 2008年11月. 八巻陽子, 重永章, 大髙章 :
分子内redox反応を利用したフルオロアルケンジペプチドイソスターの合成,
第34回反応と合成の進歩シンポジウム, 2008年11月. Yoshitake Sumikawa, Shugo Tsuda, Akira Shigenaga and Akira Otaka :
The application of peptide thioacids to NCL-type sequential condensation of peptide fragments,
The 45th Japanese Peptide Symposium, Oct. 2008. Akira Shigenaga, Naomi Nishioka, Jun Yamamoto, Hiroko Hirakawa, Yoshitake Sumikawa, Keiko Yamaguchi and Akira Otaka :
Influence of an amino acid sequence on kinetics of peptide bond cleavage reaction induced by a stimulus-responsive amino acid,
The 45th Japanese Peptide Symposium, Oct. 2008. Yoko Yamaki, Akira Shigenaga and Akira Otaka :
Synthesis of fluoroalkene dipeptide isostere utilizing intramolecular redox reaction,
The 45th Japanese Peptide Symposium, Oct. 2008. Shugo Tsuda, Nami Maeda, Kiyomi Bando, Akira Shigenaga and Akira Otaka :
Synthesis of peptide thioester using N-substituted aniline derivatives,
The 45th Japanese Peptide Symposium, Oct. 2008. 住川栄健, 津田修吾, 重永章, 大髙章 :
チオカルボン酸を利用した化学的蛋白質合成法の開発に関する研究,
第24回若手化学者のための化学道場, 2008年9月. Shugo Tsuda, Akira Shigenaga, Daisuke Tsuji, Naomi Nishioka, Yoshitake Sumikawa, Kouji Itou and Akira Otaka :
Development of UV irradiation-responsive amino acid with peptide bond cleavage ability and its application to a nucleocytoplasmic shuttle peptide,
第22回内藤コンファレンス, Sep. 2008. 重永章, 西岡直美, 山本純, 大髙章 :
任意の刺激応答型ペプチド結合切断デバイスの開発,
日本ケミカルバイオロジー研究会第3回年会, 2008年5月. 津田修吾, 前田奈美, 重永章, 大髙章 :
人工プロテインスプライシングシステムにおけるペプチド結合切断のための側鎖修飾型アスパラギンの検討,
日本薬学会年会, 2008年3月. 重永章, 辻大輔, 西岡直美, 山本純, 津田修吾, 伊藤孝司, 大髙章 :
ペプチド結合切断能を有する光応答型アミノ酸の開発と核-細胞質シャトルペプチドへの応用,
日本薬学会年会, 2008年3月. Akira Shigenaga, Daisuke Tsuji, Nishioka Naomi, Tsuda Shugo, Kouji Itou and Akira Otaka :
Development of stimulus-responsive amino acid with peptide bond-cleavage ability and its application to a nucleocytoplasmic shuttle peptide,
第44回ペプチド討論会, Nov. 2007. 山口圭子, 辻貴志, 佐々木義一, 重永章, 大髙章 :
有機銅試薬を用いたSN2'型アリル化反応の開発とプロリン型ジペプチドイソスターの合成,
第46回日本薬学会病院薬剤師会中国四国支部学術大会, 2007年11月. 八巻陽子, 住川栄健, 重永章, 大髙章 :
N-ヘテロサイクリックカルベンを利用したフルオロアルケンイソスターの合成,
第46回日本薬学会病院薬剤師会中国四国支部学術大会, 2007年11月. 津田修吾, 前田奈美, 西岡直美, 重永章, 大髙章 :
機能性ペプチドの創製を目指したアミド結合切断法の開発,
第46回日本薬学会病院薬剤師会中国四国支部学術大会, 2007年11月. 重永章, 辻大輔, 西岡直美, 津田修吾, 伊藤孝司, 大髙章 :
ペプチド結合切断能を有する刺激応答型アミノ酸の開発と核-細胞質シャトルペプチドへの展開,
第33回反応と合成の進歩シンポジウム, 2007年11月. 重永章, 辻大輔, 津田修吾, 伊藤孝司, 大髙章 :
刺激応答型アミノ酸を利用した核-細胞質シャトルペプチドの開発,
日本ケミカルバイオロジー研究会第2回年会, 2007年5月. 八巻陽子, 重永章, 富田健嗣, 鳴海哲夫, 藤井信孝, 大髙章 :
N-ヘテロサイクリックカルベンによる分子内レドックス反応を利用したフルオロアルケンイソスターの合成,
日本薬学会年会, 2007年3月. 重永章, 津田修吾, 大髙章 :
外部刺激応答型ペプチドプロセシングデバイスの開発,
日本薬学会年会, 2007年3月. 重永章, 新宅沙織, 大髙章 :
外部刺激応答型ペプチドの合成と外部刺激応答能の検討,
第32回反応と合成の進歩シンポジウム, 2006年12月. 重永章, 新宅沙織, 大髙章 :
光刺激応答型ペプチドの開発と速度論的検討,
第7回長井長義記念シンポジウム, 2006年9月. 重永章, 大髙章 :
蛋白質機能の時空間的制御を目指した外部刺激応答型ペプチドの開発,
日本薬学会年会, 2006年3月.

研究会・報告書: 田原強, 篠﨑千穂, 吉丸哲郎, 毛利浩太, 傳田将也, 大谷環樹, 片桐豊雅, 大髙章, 向井英史, 崔翼龍 :
PETを用いた脂質化抗がんペプチドの動態解析,
日本分子イメージング学会, 2024年5月. 岩本和也, 猪熊翼, 坂本健, 佐藤浩平, 重永章, 大髙章 :
NCL法を利用したペプチド–タンパク質コンジュゲーション法の開発研究,
第6回夏の生物系勉強会, 2015年8月. 小宮千明, 猪熊翼, 重永章, 大髙章 :
タンパク質機能の時空間的制御を指向したペプチド結合切断能を有する刺激応答型アミノ酸の開発,
文部科学省科学研究費補助金新学術領域研究「融合マテリアル」第10回若手スクール, 2014年5月. Akira Shigenaga and Akira Otaka :
Development of traceable linker for target identification using N-sulfanylethylanilide unit,
The 2nd International Symposium on Chemical Biology of Natural Products: Target ID and Regulation of Bioactivity, Oct. 2013. 粟飯原圭佑, 重永章, 辻耕平, 佐藤浩平, 大髙章 :
タンパク質化学合成を指向した多成分ペプチドフラグメント縮合法の開発,
文部科学省科学研究費補助金新学術領域研究「融合マテリアル」第5回若手スクール, 2012年11月. 重永章, 山本純, 前田奈美, 佐藤陽一, 山内あい子, 大髙章 :
標的タンパク質の精製およびラベル化を可能とするトレーサブルリンカーの開発,
新学術領域研究「天然物ケミカルバイオロジー:分子標的と活性制御」第2回若手研究者ワークショップ, 2012年10月. Kohei Sato, Akira Shigenaga and Akira Otaka :
Native chemical ligation (NCL) without using peptide thioester,
14th Peptide Forum, Dec. 2011. Kohei Tsuji, Yoshitake Sumikawa, Akira Shigenaga and Akira Otaka :
Diversity-oriented Synthesis of CXCL14 and Its Derivatives,
The Second Decennial Meeting Between The University of Tokushima and Seoul National University on Pharmaceutical Sciences, Dec. 2010. Kohei Sato, Shugo Tsuda, Yoshitake Sumikawa, Nami Maeda, Masaya Denda, Akira Shigenaga and Akira Otaka :
Native chemical ligation utilizing N-peptidyl anilide auxiliary,
The Second Decennial Meeting Between The University of Tokushima and Seoul National University on Pharmaceutical Sciences, Dec. 2010. Keiji Ogura, Hiroko Hirakawa, Akira Shigenaga and Akira Otaka :
Synthesis of nonhydrolyzable AMPylated amino acid mimetics for revealing physiological role of AMPylated protein,
The Second Decennial Meeting Between The University of Tokushima and Seoul National University on Pharmaceutical Sciences, Dec. 2010. Jun Yamamoto, Nami Maeda, Masaya Denda, Akira Shigenaga and Akira Otaka :
Design and synthesis of recapturable cleavable linker for efficient enrichment and specific labeling of target proteins,
The Second Decennial Meeting Between The University of Tokushima and Seoul National University on Pharmaceutical Sciences, Dec. 2010. Ko Morishita, Keiko Yamaguchi, Hao Ding, Akira Shigenaga and Akira Otaka :
Development of stimulus responsive thiol releasing device for controlling activity of cysteine protease,
The Second Decennial Meeting Between The University of Tokushima and Seoul National University on Pharmaceutical Sciences, Dec. 2010. Akira Shigenaga and Akira Otaka :
Development of stimulus-responsive amino acid with peptide bond-cleavage ability and its application for controlling peptidyl function,
The Second Decennial Meeting Between The University of Tokushima and Seoul National University on Pharmaceutical Sciences, Dec. 2010. 重永章, 大髙章 :
刺激応答型アミノ酸の開発とペプチド機能制御への展開,
第6回HBS月例セミナー, 2009年10月.

特許: 研究者総覧に該当データはありませんでした。
作品: 研究者総覧に該当データはありませんでした。
補助金・競争的資金: GIP/GLP-1受容体共刺激による血糖降下・体重減少作用増強メカニズムの解明 (研究課題/領域番号: 24K11712 )
相互作用タンパク質の同定・トポロジー解析を指向した光活性型クロスリンカーの開発 (研究課題/領域番号: 24K09728 )
コンディショナルプロテオミクスの課題を克服するラジカル再結合型ラベル化試薬の創出 (研究課題/領域番号: 24K09722 )
ロッセン転位による分子内Redox反応を基盤とするalpha炭素酸化ペプチド合成の革新 (研究課題/領域番号: 23K18187 )
カチオン脱離性スルホキシドによる側鎖修飾反応の開発と酸化修飾ペプチド合成への展開 (研究課題/領域番号: 23K27300 )
プロスタノイドEP4受容体の恒常的活性による細胞増殖速度調整メカニズムの解明 (研究課題/領域番号: 23K06149 )
翻訳後修飾部分に多様性を有するタンパク質ライブラリ精密構築への挑戦 (研究課題/領域番号: 20K21483 )
乳がんにおける休眠抑制因子群再活性化を利用した創薬研究 (研究課題/領域番号: 17K19601 )
細胞内メチル化制御分子可視化のための蛍光プローブの開発と展開研究 (研究課題/領域番号: 17K19492 )
乳がん細胞における新規エストロゲン受容体活性制御分子BIG3の病態機能の解明 (研究課題/領域番号: 16H05153 )
次世代タンパク性医薬品開発に向けた反応システム系の開発と展開 (研究課題/領域番号: 16H02611 )
半合成抗体様分子創製法の開拓研究 (研究課題/領域番号: 15K14979 )
真に実用的なペプチド・タンパク質機能制御を可能とする刺激応答型アミノ酸の開発 (研究課題/領域番号: 15K07858 )
デュアルエフェクト応答型タンパク質ラベル化試薬の開発 (研究課題/領域番号: 25670058 )
アポリポタンパク質によるHDL産生・代謝調節機構の物理化学的基盤解明と創薬展開 (研究課題/領域番号: 25293006 )
分子標的探索のための化学選択的修飾部位内在型リンカーの開発 (研究課題/領域番号: 24102521 )
創薬基盤確立に向けた効率的人工タンパク質化学合成法の開拓 (研究課題/領域番号: 24390026 )
高選択的速度論支配ペプチド結合形成反応を基盤とするタンパク質化学合成法の開拓 (研究課題/領域番号: 23659055 )
天然物・生物有機化学を基盤とする創薬標的タンパク質同定効率化法の開拓と応用展開 (研究課題/領域番号: 23390026 )
触媒的タンパク質機能欠失法の開拓 (研究課題/領域番号: 21390031 )
化学的アミド結合切断を基盤とする時空間制御型タンパク質機能発現調節法の開発 (研究課題/領域番号: 19651096 )
不溶性膜タンパク質化学合成に向けた化学的基盤の確立と応用 (研究課題/領域番号: 18390006 )
ウイルスの共通分子機構を標的とする抗ウイルスペプチドの開発戦略の創製 (研究課題/領域番号: 18032051 )
ウイルスの共通分子機構を標的とする抗ウイルスペプチドの開発戦略の創製 (研究課題/領域番号: 17035042 )
人工スプライシングシステムの構築と不溶性蛋白質合成への展開 (研究課題/領域番号: 15659026 )
ヘリックス性ペプチドの機能面区化と抗HIV剤への展開 (研究課題/領域番号: 15390037 )
CXCR4とgp41をダブルターゲットとした人工設計型HIV侵入阻害剤の創製研究 (研究課題/領域番号: 15019049 )
ケミカルレセプトームの開発と応用 (研究課題/領域番号: 14657590 )
ペプチド・蛋白質化学を基盤とするゲノム・プロテオーム情報収斂型創薬研究 (研究課題/領域番号: 14207099 )
HIV外皮蛋白断片gp41-C34を基にした人工設計型細胞融合阻害剤の創製研究 (研究課題/領域番号: 14021051 )
有機銅を利用した効率的フルオロアルケンジペプチドイソスターの合成研究 (研究課題/領域番号: 13672210 )
HIV外皮蛋白断片gp41-C34を基にした人工設計型細胞融合阻害剤の創製研究 (研究課題/領域番号: 13226055 )
非ウイルス性ベクターによる膵癌治療法の開発 (研究課題/領域番号: 12877192 )
高選択的CXCR4-ケモカイン受容体拮抗剤を基盤分子とする新規抗HIV剤の創製 (研究課題/領域番号: 12557218 )
細胞周期調節機能を有するペプチドの創製と抗がん剤への展開研究 (研究課題/領域番号: 12217073 )
マラリア原虫の増殖機構をターゲットとする新規マラリア治療薬の開発研究 (研究課題/領域番号: 11147213 )
ランタノイド金属を用いた2級非水解性リン酸化アミノ酸の合成と生理活性に関する研究 (研究課題/領域番号: 10671988 )
ペプチドリード医薬品の実践的開発戦略研究 (研究課題/領域番号: 10470491 )
(E)-アルケンペプチドイソスターを探索子とする高活性GRP拮抗剤の創製 (研究課題/領域番号: 10169235 )
実用化を指向した高効率且つ高選択的な抗腫瘍活性プソイド・ペプチド医薬品の開発 (研究課題/領域番号: 09557179 )
(E)-アルケンペプチドイソスターを探索子とする高活性GRP拮抗剤の創製 (研究課題/領域番号: 09273234 )
ヒトがん細胞におけるMAPキナーゼカスケードの異常-細胞がん化との相関 (研究課題/領域番号: 09254253 )
生体内情報伝達機構解明を指向したホスファターゼ抵抗性リン酸化ペプチドの合成 (研究課題/領域番号: 09249210 )
二段階脱保護法による実用的リン酸化ペプチド・タンパク質の合成法の開発に関する研究 (研究課題/領域番号: 08672421 )
強力なボンベシンアンタゴニスト活性を持つペプチドイソスターの合成と抗癌剤への展開 (研究課題/領域番号: 08457621 )
MAPキナーゼカスケードを構成するシグナル分子を標的とした細胞増殖阻害物質の検索 (研究課題/領域番号: 08266258 )
生体内情報伝達機構解明を指向したホスファターゼ抵抗性リン酸化ペプチドの合成 (研究課題/領域番号: 08260210 )
新規最終脱保護系を用いた高効率リン酸化ペプチドの合成法の開発に関する研究 (研究課題/領域番号: 07772094 )
生体内情報伝達機構解明を指向したホスファターゼ抵抗性リン酸化ペプチドの合成 (研究課題/領域番号: 07268209 )
ペプチドの高効率合成法の開発と抗ウイルス作用を有する内因性生体防御ペプチドの合成 (研究課題/領域番号: 05671748 )
アスパルチルプロテア-ゼ阻害剤を基礎としたエイズ治療薬の開発研究 (研究課題/領域番号: 02670952 )
研究者番号（20201973）による検索

その他: 研究者総覧に該当データはありませんでした。

研究者総覧で最新データを確認する

2024年12月19日更新

専門分野・研究分野: 生物有機化学
有機合成化学
ペプチド・タンパク質化学
ケミカルバイオロジー
所属学会・所属協会: 日本薬学会
日本ペプチド学会
日本ペプチド学会 [2018年4月〜2020年3月])
委員歴・役員歴: 日本薬学会 (副会頭 [2015年4月〜2017年3月])
日本ペプチド学会 (理事 [2008年4月〜2014年3月])
日本ペプチド学会 (評議員 [2014年4月〜2016年3月])
日本ペプチド学会 (理事(会計) [2018年4月〜2020年3月])
日本薬学会 (創薬セミナー委員会委員長 [2018年4月〜2021年3月])
日本薬学会 (医薬化学部会常任世話人 [2022年4月〜2026年3月])
日本ペプチド学会 (評議員 [2022年4月〜2024年3月])
日本ペプチド学会 (会長 [2024年4月〜2026年3月])
日本薬学会 (化学系薬学部会副部会長 [2023年4月〜2025年3月])
受賞: 2012年2月, 有機合成化学協会アステラス製薬・生命有機化学賞 (公益社団法人有機合成化学協会)
2018年2月, 康楽賞 (公益財団法人康楽会)
2022年4月, 2022年度日本薬学会学会賞 (日本薬学会)
2023年7月, 2023年度日本ペプチド学会学会賞 (日本ペプチド学会)
活動: 評議員 (2010年4月〜2013年3月)
大学院医歯薬学研究部運営協議会 (2012年4月〜2017年3月)
薬学部長 (2013年4月〜2017年3月)
薬科学教育部長 (2013年4月〜2017年3月)
医歯薬学研究部副研究部長 (2013年4月〜2017年3月)
薬学部運営会議委員長 (2013年4月〜2017年3月)
総合薬学センター長 (2013年4月〜2017年3月)
臨床薬学実務教育室運営委員会委員長 (2013年4月〜2017年3月)
総合薬学研究推進室運営委員会委員長 (2013年4月〜2017年3月)
薬学部進路委員会委員長 (2013年4月〜2017年3月)
長井長義資料委員会委員長 (2013年4月〜2017年3月)
薬学部国際交流委員会委員長 (2013年4月〜2017年3月)
教育研究助成奨学金運営委員会委員長 (2013年4月〜2017年3月)
寄附物品等受入審査委員会委員長 (2013年4月〜2017年3月)
徳島大学大学院医歯薬学研究部薬学系分野の教授選考分野に関するあり方委員会委員長 (2013年4月〜2017年3月)
附属図書館長 (2023年4月〜2025年3月)

リサーチマップで最新データを確認するＪグローバルで最新データを確認する

2024年12月15日更新

2024年12月14日更新

Ｊグローバル

Jグローバル最終確認日: 2024/12/14 01:17
氏名（漢字）: 大高章
氏名（フリガナ）: オオタカアキラ
氏名（英字）: Otaka Akira
所属機関: 徳島大学教授

リサーチマップ

researchmap最終確認日: 2024/12/15 01:24
氏名（漢字）: 大高章
氏名（フリガナ）: オオタカアキラ
氏名（英字）: Otaka Akira
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登録日時: 2010/1/26 00:00
更新日時: 2024/10/2 15:01
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所属ID: 0344000000
所属: 徳島大学
部署: 大学院医歯薬学研究部機能分子合成薬学分野
職名: 教授
学位: 薬学博士
学位授与機関: 京都大学
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受賞
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ＫＡＫＥＮで最新データを確認する

2024年12月14日更新

研究者番号: 20201973

所属（現在）: 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 教授

所属（過去の研究課題 情報に基づく）*注記: 2023/4/1 – 2024/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 教授
2017/4/1 – 2021/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学域), 教授
2016/4/1 – 2018/4/1 : 徳島大学, 大学院医歯薬学研究部(薬学系), 教授
2015/4/1 – 2016/4/1 : 徳島大学, 大学院医歯薬学研究部, 教授
2011/4/1 – 2014/4/1 : 徳島大学, ヘルスバイオサイエンス研究部, 教授
2005/4/1 – 2013/4/1 : 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授
2007/4/1 : 徳島大学, 大学院・ヘルスバイオサイエンス研究院, 教授
2007/4/1 : 徳島大学, 大学院・ヘルスバイオサイエン研究部, 教授
2005/4/1 – 2006/4/1 : 徳島大学, 大学院ヘルスバイオサイエンス研究部, 教授
1997/4/1 – 2004/4/1 : 京都大学, 薬学研究科, 助教授
2001/4/1 : 京都大学, 薬学研究科(研究院), 助教授
1999/4/1 : 京都大学, 大学院・薬学研究科, 助教授
1997/4/1 : 京都大学, 大学院・薬学研究科, 助教授
1995/4/1 – 1996/4/1 : 京都大学, 薬学部, 助教授
1993/4/1 – 1994/4/1 : 京都大学, 薬学部, 助手
1990/4/1 – 1991/4/1 : 京都大学, 薬学部, 助手

審査区分/研究分野

研究代表者

医学 / 薬学 / 化学系薬学
生物系 / 医歯薬学 / 薬学 / 創薬化学
生物系 / 医歯薬学 / 薬学 / 化学系薬学
総合・新領域系 / 複合新領域 / 生体分子科学 / 生物分子科学
薬学およびその関連分野
生物系
理工系
中区分47:薬学およびその関連分野
小区分47010:薬系化学および創薬科学関連
小区分47050:環境および天然医薬資源学関連
合同審査対象区分:小区分47010:薬系化学および創薬科学関連、小区分47050:環境および天然医薬資源学関連

研究代表者以外

医学 / 外科 / 消化器外科学
医学 / 薬学 / 医薬分子機能学
生物系 / 医歯薬学 / 薬学 / 創薬化学
医学 / 薬学 / 化学系薬学
生物系 / 医歯薬学 / 薬学 / 物理系薬学
生物系 / 医歯薬学 / 薬学 / 化学系薬学
生物系 / 医歯薬学 / 基礎医学 / 病態医化学
腫瘍学およびその関連分野
生物系
中区分47:薬学およびその関連分野
小区分47040:薬理学関連
小区分47010:薬系化学および創薬科学関連
小区分54040:代謝および内分泌学関連

キーワード

研究代表者

リン酸化 / リン酸化ペプチド / ペプチド合成 / 最終脱保護 / ホスファターゼ / 細胞内情報伝達 / ホスファターゼ抵抗性 / ジメチルホスフェートアミノ酸 / ペプチドイソスター / アルケン / GRP拮抗剤 / ペプチドリード医薬品 / (E)-アルケン型ジペプチドイソスター / GRP / ボンベシン / 有機銅試薬 / 還元的アルキル化 / パラジウム触媒 / リン酸化アミノ酸 / 非水解性リン酸化アミノ酸 / ペプチドミメティック / 細胞周期 / 不溶性蛋白質 / スプライシング / ペプチドチオエステル / インテイン / 膜タンパク質 / 光切断型保護基 / イシテイン / 膜蛋白質 / ウイルス / 感染症 / 有機化学 / 生体分子 / 蛋白質 / 膜融合 / ペプチド / 不溶性膜タンパク質 / エクステイン / アシル転位 / アシル転移 / アミド結合 / タンパク質機能 / 外部刺激応答型アミノ酸 / ペプチド結合切断 / 標的タンパク質 / ホスファターゼ抵抗性リン酸化アミノ酸 / タンパク質 / チオエステル / タンパク濃縮 / 刺激応答型アミノ酸 / ペプチド等価体 / デグロン / 速度論的支配 / Native Chemical Ligation / タンパク質合成 / 速度論的反応 / NCL / 速度論支配 / アビジン / ビオチン / アミド結合切断 / タンパク質化学合成 / ラベル化 / N-Sアシル転移 / タンパク質ラベル化 / ケミカルバイオロジー / 固相合成 / ジスルフィド結合 / 生体防御ペプチド / プロテグリン / デフェンシン / Avidin-biotin / アフィニティークロマト / Solid-phase synthesis / Disulfide bond / Self-defense peptide / Protegrin / Defensin / Affinity purification / フラグメント結合 / phosphoamino acid / phosphopeptides / peptide synthesis / final deprotection / dimethylphosphono amino acids / クロスカップリング反応 / 不斉補助基 / フルオロアルケン / ジペプチドイソスター / ヨウ化サマリウム / 一電子還元剤 / Sm-ジエノラート / ジペプチドイスター / ヨウ価サマリウム / organocopper reagents / fluoroalkene / dipeptide isosteres / samarium diiodide / one-electron reducing agent / samarium dienolate / HIV-1 / α-helix / 抗ウイルス剤 / SARS-CoV / a-helix / SARS / membrane fusion / anti-viral agents / peptide / アシル基転移反応 / 抗体医薬 / ペプチドヒドラジド / 配列選択的反応 / タンパク性医薬 / タンパク質修飾 / カルボキシペプチダーゼ / タンパク性医薬品 / タンパク質半合成 / プロテアーゼ / タンパク質チオエステル / タンパク質ヒドラジド / 配列特異的反応 / 生体内メチル化 / 蛍光プローブ分子 / 生体反応可視化 / アデノシルホモシステイン / 蛍光プローブ / S-アデノシルホモシステイン / ロッセン転位 / 分子内Redox反応 / イミン / アルファー修飾ペプチド / 修飾反応 / 保護システイン / スルホキシド / スルフェニル化 / 側鎖修飾

研究代表者以外

細胞がん化 / ヒトがん細胞 / MAPキナーゼ / MAPキナーゼ・キナーゼ / Ras / 阻害剤 / フラボン / MEK阻害剤 / 増殖阻害 / アポトーシス / pp125^<FAK> / マラリア / Plasmodium falciparum / Plasmepsin II / aza-Payne転位反応 / ChondroitinsulfateA / Duffy-結合様ドメイン / マラリアワクチン / 基質遷移状態模倣型酵素阻害剤 / トロージャンペプチド / p16 / Bcl-X遺伝子 / アンチセンス・オリゴヌクレオチド / 遺伝子治療 / 膵癌 / HIV外皮蛋白質gp41 / 6-helical bundle構造 / 膜融合阻害剤 / 薬剤耐性型抗HIV剤 / de novoデザイン / 6 helical bundle構造 / SC34 / 人工設計 / X線結晶解析 / CXCR4アンタゴニスト / T140 / ケモカインレセプター / 受容体 / 膜タンパク質 / ペプチドチオエステル / CXCR4 / 脂質二重膜 / gp41 / タンパク質合成 / HIV / 脂質膜 / リポソーム / HIV侵入阻害剤 / T細胞指向性HIV-1 / de novo設計 / 環状ペプチド / 低分子化 / 非ペプチド化 / 天然物 / 不斉合成 / 創薬 / 標的タンパク / ケミカルバイオロジー / ベイト分子 / プルダウン法 / プロテオミクス / 標的タンパク質 / 細胞接着 / プルダウンアッセイ / アスパーギライド / 細胞毒性 / ビオチン / 光親和性標識 / クリックケミストリー / 標的タンパク同定 / エイズウイルス / アスパルチルプロテア-ゼ / 有機銅ールイス酸複合剤 / トランスオレフィン型イソスタ- / Fmoc型固相法 / アルパルチルプロテア-ゼ / AIDS Virus / Aspartyl protease / Inhibitor / organocopper-Lewis Acid Complex / Trans olefin type isostere / Fmoc-Based Solid Phase Synthesis / 有機銅試薬 / 活性化アジリジンエノエ-ト / 0価パラジウム / (E)-アルケンジペプチドイソスター / ボンベシンアンタゴニスト / アミラーゼ分泌抑制 / 抗腫瘍活性 / 立体制御合成プロセス / キラルプール / 立体特異的1,3-不斉転移 / (E)-アルケン型ジペプチドイソスター / 遷移金属触媒による異性化反応 / 膵癌細胞増殖抑制 / Organocopper Reagents / Activated Aziridinyl Enoates / Palladium(0) / (E)-Alkene Dipeptide Isosters / Bombesin Antagonist / Inhibition of Amylase Release / Anti-Cancer Activity / Stereocontrolled Synthetic Route / 有機銅化合物 / ボンベシン・アンタゴニスト / SN2型開環反応 / アルケンイソスター / アジリジニル・エノエイト / ビニルアジリジン / 有機パラジウム化合物 / アリルパラジウム錯体 / トリプトファン・イソスター / トリプトフアン・イソスター / Organocopper Compound / SN2-type Ring-Opening / Alkene Isostere / Aziridinylenoate / Vinylaziridine / Organopalladium Compound / Allylpalladium Complex / 立体的選択的合成反応 / アスパルチルプロテアーゼ / 基質遷移状態模倣型阻害剤 / aza-Payne転位 / β-セクレターゼ / HIVプロテアーゼ / アルケン型ジペプチドイソスター / ペプチドイソスター / ゲノム情報集約型ライブラリー / 立体配座固定 / αVβ3インテグリン拮抗剤剤 / 癌 / アルツハイマー型痴呆症 / エイズ / 有機亜鉛-銅複合試薬 / ペプチドリード医薬品 / Ru-触媒メタセシス閉環反応 / グローバル配座固定 / HIVプロテアーゼ阻害剤 / β-secretase / 多剤耐性HIV型プロテアーゼ / オレフィンメタセシス閉環反応 / (E)-Alkcnc型dipcptidcisostcrc / 非天然型アミノ酸誘導体 / 基質遷移状態ミミック構造 / 遷移金属触媒 / ケモカインアンタゴニスト / Stereoselective Synthesis / Aspartyl Protease / Substrate Transition State Mimic / aza-Payne Rearrangement / β-Secretase / HIV-protease / Organocopper Reagent / Alkene-type tipeptide isostere / HIV進入阻害剤 / CXCR4ケモカインレセプター / T細胞指向性HIV / 多剤耐性HIV / de novo分子設計 / 環状ペンタペプチドライブラリー / ホモロジーモデリング / 機能性CXCR4変異体 / T140-CXCR4ドッキング解析 / FC131 / gp41-標的型HIV-Cell膜融合阻害剤 / SC34EK / spring8 / CXCR4拮抗剤 / HIV-cell融合阻害剤 / 多剤耐性克服型抗HIV剤 / 二価官能性抗HIV剤 / HIV第二受容体拮抗剤 / CXCR4ケモカイン受容体 / T140立体構造 / 逆転写酵素阻害 / エイス / コンビナトリアル合成 / 有用金属試薬 / anti-HIV agents / chemokine receptor / T-cell line-tropic HIV / low molecular weight CXCR4 antagonists / HIV-cell fusion inhibitors / de novo design / ゲノム科学 / 創薬研究 / ペプチド化学 / Chemical Ligation / 7回膜貫通型GPCR / Constitutively Active Receptor Technology / ゲノム情報 / 蛋白質化学 / 創薬テンプレート / 7回膜貫通型レセプター / HIV感染 / Germinal Center / リウマチ / ゲノム / プロテオーム / SARS Corona Virus / 7TM-GPCR / αVβ3-integrin / ユニバーサル創薬テンプレート / genome science / drug discovery / peptide-isosteres / Peptide Chemistry / CXCR4 antagonist / chemical ligation / G-protein coupled receptor / アポリポタンパク質 / HDL / コンフォメーション / 抗体 / アミロイド / 糖鎖 / ＨＤＬ / コレステロール代謝 / 脂質異常症 / アミロイドーシス / ABCトランスポーター / トリメチルロック / 機能制御 / ペプチド / タンパク質 / 刺激応答 / ラクトン化 / アミド結合切断 / ペプチド結合切断 / 活性制御 / 刺激応答型アミノ酸 / breast cancer / estrogen signaling / tumor suppressor / phosphorylation / dephosphorylation / oncogenic signaling / mitochondrial regulation / 生体機能利用 / multistep carcinogenesis / タンパク相互作用阻害 / 乳がん / ミトコンドリア / がん抑制因子 / がん特異的発現亢進因子 / HER2 / タンパク質半合成 / ネイティブケミカルライゲーション / タンパク質化学 / 翻訳後修飾 / タンパク質化学合成 / タンパク質ライブラリ / Native Chemical Ligation / 大腸癌制御メカニズム解明 / タンパク質ラベル化 / クロスリンク質量分析法 / プロテオミクス解析 / タンパク質間相互作用 / インクレチン / GLP-1 / GIP

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2021年10月8日

新薬候補物質の創出を指向した多様な側鎖構造を持つアミノ酸およびペプチドの新規合成法開発

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