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Exploring catalytic functions of selenocysteine

Research Project

Project/Area Number 17K05792
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Organic chemistry
Research InstitutionTokai University

Principal Investigator

Iwaoka Michio  東海大学, 理学部, 教授 (30221097)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsセレン / セレノシステイン / 酵素モデル / ペプチド合成 / セレノインスリン / セレノグルタチオン / 環状ペプチド / アミノ酸 / インスリン / スレオニン / 不飽和カルボン酸 / 不飽和ラクトン / 光学分割 / グルタチオン / 不斉触媒 / 金属錯体 / ペプチド / 抗酸化剤
Outline of Final Research Achievements

The aim of this research project was to explore the catalytic functions of selenocysteine. In this project, the following outcomes were obtained. An easy and efficient method to produce selenocysteine derivatives from natural amino acid serine was established. Using the obtained selenocysteine derivatives, novel catalytic organic transformation reactions were found, mimics of selenoenzymes were developed, a convenient synthetic method was established for selenoglutathione, a selenoinsulin analog was synthesized, and the synthesis of cyclic selenopeptides was achieved by application of intramolecular native chemical ligation.

Academic Significance and Societal Importance of the Research Achievements

セレノシステインは遺伝子情報によってタンパク質に直接組み込まれる第21番目のアミノ酸である。セレノシステインを活性中心に含むセレン酵素は多数知られているが、これまでその反応メカニズムの詳細が酵素に近いアミノ酸モデルを用いて研究されたことはほとんどなかった。本研究では、セレノシステイン誘導体を用いた研究によって、その一端を明らかにすることができた。研究成果は創薬への応用が期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (50 results)

All 2019 2018 2017 Other

All Int'l Joint Research (9 results) Journal Article (17 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 15 results,  Open Access: 8 results) Presentation (20 results) (of which Int'l Joint Research: 9 results,  Invited: 6 results) Book (1 results) Remarks (3 results)

  • [Int'l Joint Research] コペンハーゲン大学(デンマーク)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] 理科大学院/バーバ原子力研究所(インド)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] マックスプランク生化学研究所(ドイツ)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] コペンハーゲン大学(デンマーク)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] 理科大学院(インド)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] マックスプランク生化学研究所(ドイツ)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] コペンハーゲン大学(デンマーク)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] 理科大学院/バーバ原子力研究所(インド)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] マックスプランク生化学研究所(ドイツ)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Oxidative folding pathways of bovine milk β‐lactoglobulin with odd cysteine residues2019

    • Author(s)
      Iwaoka Michio、Mitsuji Takumi、Shinozaki Reina
    • Journal Title

      FEBS Open Bio

      Volume: 9 Issue: 8 Pages: 1379-1391

    • DOI

      10.1002/2211-5463.12656

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Free radical induced selenoxide formation in isomeric organoselenium compounds: the effect of chemical structures on antioxidant activity2019

    • Author(s)
      Singh Beena G.、Kumar Pavitra、Phadnis P.、Iwaoka Michio、Priyadarsini K. Indira
    • Journal Title

      New Journal of Chemistry

      Volume: 43 Issue: 34 Pages: 13357-13362

    • DOI

      10.1039/c9nj02227a

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Oxidative Protein Folding Using trans-3,4-Dihydroxyselenolane Oxide2019

    • Author(s)
      Arai Kenta、Iwaoka Michio
    • Journal Title

      Methods Mol Biol.

      Volume: 1967 Pages: 229-244

    • DOI

      10.1007/978-1-4939-9187-7_14

    • ISBN
      9781493991860, 9781493991877
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of selenocysteine-containing dipeptides modeling the active site of thioredoxin reductase2019

    • Author(s)
      Shimodaira Shingo、Iwaoka Michio
    • Journal Title

      Phosphorus, Sulfur, and Silicon and the Related Elements

      Volume: 194 Issue: 7 Pages: 750-752

    • DOI

      10.1080/10426507.2019.1603721

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modeling Thioredoxin Reductase‐Like Activity with Cyclic Selenenyl Sulfides: Participation of an NH???Se Hydrogen Bond through Stabilization of the Mixed Se?S Intermediate2019

    • Author(s)
      Arai Kenta、Matsunaga Takahiko、Ueno Haruhito、Akahoshi Nozomi、Sato Yuumi、Chakrabarty Gaurango、Mugesh Govindasamy、Iwaoka Michio
    • Journal Title

      Chemistry ? A European Journal

      Volume: 25 Issue: 55 Pages: 12751-12760

    • DOI

      10.1002/chem.201902230

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Characterization and optimization of two-chain folding pathways of insulin via native chain assembly2018

    • Author(s)
      Arai Kenta、Takei Toshiki、Shinozaki Reina、Noguchi Masato、Fujisawa Shouta、Katayama Hidekazu、Moroder Luis、Ando Setsuko、Okumura Masaki、Inaba Kenji、Hojo Hironobu、Iwaoka Michio
    • Journal Title

      Communications Chemistry

      Volume: 1 Issue: 1 Pages: 26-26

    • DOI

      10.1038/s42004-018-0024-0

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of Crystal Structure on Up-conversion Luminescence in Er3+/Yb3+ Co-doped SrTa4O112018

    • Author(s)
      Tamura Sayaka、Iwaoka Michio、Sato Yasushi、Kobayasi Makoto、Kakihana Masato、Tomita Koji
    • Journal Title

      Chemistry Letters

      Volume: 47 Issue: 10 Pages: 1282-1284

    • DOI

      10.1246/cl.180605

    • NAID

      130007496120

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synthesis of selenocysteine-containing cyclic peptides via tandem N-to-S acyl migration and intramolecular selenocysteine-mediated native chemical ligation2018

    • Author(s)
      Shimodaira Shingo、Takei Toshiki、Hojo Hironobu、Iwaoka Michio
    • Journal Title

      Chemical Communications

      Volume: 54 Issue: 83 Pages: 11737-11740

    • DOI

      10.1039/c8cc06805d

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] インスリンの高次構造形成過程の解明-インスリン製剤の簡便な化学合成への展開2018

    • Author(s)
      荒井堅太, 岩岡道夫
    • Journal Title

      ファルマシア

      Volume: 54 Pages: 1135-1139

    • NAID

      130007539483

    • Related Report
      2018 Research-status Report
  • [Journal Article] インスリンの簡便な化学合成法の開発-未来の糖尿病治療への期待2018

    • Author(s)
      荒井堅太, 岩岡道夫
    • Journal Title

      化学

      Volume: 73 Pages: 29-33

    • NAID

      40021682274

    • Related Report
      2018 Research-status Report
  • [Journal Article] Mechanism of radioprotection by dihydroxy-1-selenolane (DHS): Effect of fatty acid conjugation and role of glutathione peroxidase (GPx)2018

    • Author(s)
      Verma Prachi、Kunwar Amit、Arai Kenta、Iwaoka Michio、Priyadarsini K. Indira
    • Journal Title

      Biochimie

      Volume: 144 Pages: 122-133

    • DOI

      10.1016/j.biochi.2017.10.021

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glutathione Peroxidase-Like Activity of Amino-Substituted Water-Soluble Cyclic Selenides: A Shift of the Major Catalytic Cycle in Methanol2017

    • Author(s)
      Arai Kenta、Tashiro Ayako、Osaka Yuui、Iwaoka Michio
    • Journal Title

      Molecules

      Volume: 22 Issue: 3 Pages: 354-354

    • DOI

      10.3390/molecules22030354

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preparation of Selenoinsulin as a Long-Lasting Insulin Analogue2017

    • Author(s)
      Kenta Arai+, Toshiki Takei+, Masaki Okumura+, Satoshi Watanabe+, Yuta Amagai, Yuya Asahina, Luis Moroder, Hironobu Hojo, Kenji Inaba, and Michio Iwaoka
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 印刷中 Issue: 20 Pages: 5522-5526

    • DOI

      10.1002/anie.201701654

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of Metal Ions, Temperature, and a Denaturant on the Oxidative Folding Pathways of Bovine α-Lactalbumin2017

    • Author(s)
      Reina Shinozaki、Michio Iwaoka
    • Journal Title

      Int. J.Mol. Sci.

      Volume: 18 Issue: 9 Pages: 1996-1996

    • DOI

      10.3390/ijms18091996

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Selenoglutathione Diselenide: Unique Redox Reactions in the GPx-Like Catalytic Cycle and Repairing of Disulfide Bonds in Scrambled Protein2017

    • Author(s)
      Shimodaira Shingo、Asano Yuki、Arai Kenta、Iwaoka Michio
    • Journal Title

      Biochemistry

      Volume: 56 Issue: 42 Pages: 5644-5653

    • DOI

      10.1021/acs.biochem.7b00751

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protein Folding in the Presence of Water-Soluble Cyclic Diselenides with Novel Oxidoreductase and Isomerase Activities2017

    • Author(s)
      Arai Kenta、Ueno Haruhito、Asano Yuki、Chakrabarty Gaurango、Shimodaira Shingo、Mugesh Govindasamy、Iwaoka Michio
    • Journal Title

      ChemBioChem

      Volume: 19 Issue: 3 Pages: 207-211

    • DOI

      10.1002/cbic.201700624

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Development of SAAP3D force field and the application to replica-exchange Monte Carlo simulation for chignolin and C-peptide2017

    • Author(s)
      Iwaoka Michio、Suzuki Toshiki、Shoji Yuya、Dedachi Kenichi、Shimosato Taku、Minezaki Toshiya、Hojo Hironobu、Onuki Hiroyuki、Hirota Hiroshi
    • Journal Title

      . Comput. Aided Mol. Design

      Volume: 31 Issue: 12 Pages: 1039-1052

    • DOI

      10.1007/s10822-017-0084-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 隣接官能基によるセレノスルフィド結合の活性化2019

    • Author(s)
      岩岡道夫, 草野修一, 松村琴依, 荒井堅太
    • Organizer
      第46回有機典型元素化学討論会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Theoretical Investigation on the Complexation of Methyl(methylselanyl)-sulfane with Acetamide, Pyrrole, Imidazole, Benzene, and Ammonium Ion2019

    • Author(s)
      Shuichi Kusano, Michio Iwaoka
    • Organizer
      14th Internactional Conference on the Chemistry of Selenium and Tellurium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Weak Interaction Network at the Active Site of Selenoenzymes2019

    • Author(s)
      Michio Iwaoka
    • Organizer
      14th Internactional Conference on the Chemistry of Selenium and Tellurium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular simnulation of short peptides using the SAAP force field: Effects of a distance-dependent dielectic constant.2018

    • Author(s)
      K. Yoshida, T. Shimosato, M. Iwaoka
    • Organizer
      10th International Peptide Synposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 水溶性セレン酸化剤を用いたウシβ-ラクトグロブリンの酸化的フォールディング経路の解析2018

    • Author(s)
      三辻匠海, 篠崎玲奈, 岩岡道夫
    • Organizer
      第45回有機典型元素化学討論会
    • Related Report
      2018 Research-status Report
  • [Presentation] Chemical synthesis of selenopeptides with modified functions2018

    • Author(s)
      M. Iwaoka
    • Organizer
      The 7th International Selenium Conference (Se2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Chemical synthesis of insulin via native chemical assembly2018

    • Author(s)
      M. Iwaoka
    • Organizer
      VII Encontro sobre Enxofre, Selenio e Telurio and 7th Workshop of SeS Redox and Catalysis
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] . Synthesis and evaluation of thioredoxin reductase model cyclic dipeptides2018

    • Author(s)
      S. Shimodaira, K. Katsumata, D. G. Churchill, M. Iwaoka
    • Organizer
      28th International Symposium on the Organic Chemistry of Sulfur (ISOCS-28)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterization of oxidative folding pathways of disulfide-containing proteins using a water-soluble selenoxide reagent2018

    • Author(s)
      M. Iwaoka
    • Organizer
      28th International Symposium on the Organic Chemistry of Sulfur (ISOCS-28)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] セレノペプチドの設計と合成2018

    • Author(s)
      岩岡道夫
    • Organizer
      . 第4回日本セレン研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] インスリンおよびセレノインスリンの化学合成と生物活性2018

    • Author(s)
      荒井堅太, 岩岡道夫
    • Organizer
      第45回有機典型元素化学討論会
    • Related Report
      2018 Research-status Report
  • [Presentation] チオレドキシンレダクターゼの活性中心を模倣したジペプチドの合成2018

    • Author(s)
      下平伸吾、勝間田憲志、岩岡道夫
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2017 Research-status Report
  • [Presentation] セレノペプチド創薬―セレノインスリンの化学合成2017

    • Author(s)
      岩岡道夫, 荒井堅太
    • Organizer
      イノベーションジャパン2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Redox chemistry of selenocysteine-containing peptides2017

    • Author(s)
      M. Iwaoka
    • Organizer
      The 6th Workshop of SeS Redox and Catalysis (WSeS-6)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] セレノペプチド創薬―セレノインスリンの化学合成2017

    • Author(s)
      岩岡道夫
    • Organizer
      東海大学総合医学研究所研修会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] セレン含有ペプチド、タンパク質の合成2017

    • Author(s)
      岩岡道夫
    • Organizer
      大阪大学蛋白質研究所セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Selenopeptide chemistry toward antioxidant drug discovery2017

    • Author(s)
      M. Iwaoka
    • Organizer
      DAE-BRNS Symposium on Selenium Chemistry & Biology (SSCB-2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] チオレドキシンレダクターゼ活性中心のモデルペプチド合成の検討2017

    • Author(s)
      勝間田憲志、下平伸吾、岩岡道夫
    • Organizer
      第44回有機典型元素化学討論会
    • Related Report
      2017 Research-status Report
  • [Presentation] L-セレノスレオニンを用いた不斉合成反応の検討2017

    • Author(s)
      大野拓也、下平伸吾、岩岡道夫
    • Organizer
      第44回有機典型元素化学討論会
    • Related Report
      2017 Research-status Report
  • [Presentation] 環状セレノペプチドによるグルタチオンペルオキシダーゼ活性中心のモデル化2017

    • Author(s)
      下平伸吾、武居俊樹、北條裕信、岩岡道夫
    • Organizer
      第44回有機典型元素化学討論会
    • Related Report
      2017 Research-status Report
  • [Book] Compounds in Biology and Medicine2017

    • Author(s)
      M. Iwaoka, K. Arai
    • Total Pages
      457
    • Publisher
      Royal Society of Chemistry
    • ISBN
      9781788010290
    • Related Report
      2017 Research-status Report
  • [Remarks] Press Release: 新規人工インスリン「セレノインスリン」の化学合成と機能解明に成功

    • URL

      http://www.protein.osaka-u.ac.jp/achievement/press-release

    • Related Report
      2017 Research-status Report
  • [Remarks] 新規人工インスリン「セレノインスリン」の化学合成と機能解明に成功

    • URL

      https://www.tohoku.ac.jp/japanese/2017/04/press20170411-01.html

    • Related Report
      2017 Research-status Report
  • [Remarks] セレン原子が切り開く、インスリン化学合成と機能の向上を目指した新しい道筋

    • URL

      https://academist-cf.com/journal/?p=4501

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

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