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Chemical synthesis of protein via simultaneous ligation of multiple peptide segments on DNA scaffold

Research Project

Project/Area Number 18K05313
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37010:Bio-related chemistry
Research InstitutionNagoya University

Principal Investigator

Hayashi Gosuke  名古屋大学, 工学研究科, 准教授 (40648268)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsタンパク質化学合成 / ペプチド連結反応 / DNA templated chemistry
Outline of Final Research Achievements

We have developed a novel peptide ligation strategy harnessing the two intrinsic characteristics of oligodeoxynucleotides (ODNs), i.e., their hydrophilicity and hybridization ability, which allowed an increase in the water solubility of peptides and the reaction kinetics due to the proximity effect, respectively. Peptide–ODN conjugates cleavable to regenerate native peptide sequences were synthesized using novel lysine derivatives containing conjugation handles and photolabile linkers, via solid-phase peptide synthesis and subsequent conjugation to 15-mer ODNs. Two complementary conjugates were applied to carbodiimide-mediated peptide ligation on a DNA scaffold and the subsequent DNA removal was conducted by photoirradiation in a traceless fashion.

Academic Significance and Societal Importance of the Research Achievements

本研究成果によって、従来mMオーダーで行う必要の合ったペプチド連結反応がサブnMの濃度で実施可能であることを示すことができた。またDNAの親水性によって疎水性ペプチド断片の水溶性向上させ、かつ低濃度で連結反応を行うことで、これまで連結反応に用いることが困難であった疎水性ペプチドを連結することができる新しい技術となった。これにより、これまでより多様なタンパク質を化学的に合成できる可能性があり、ライフサイエンス研究だけでなく、医薬学研究の発展にも寄与することが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (28 results)

All 2021 2020 2019 2018

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 4 results) Presentation (14 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results) Book (1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Organoruthenium-Catalyzed Chemical Protein Synthesis to Elucidate the Functions of Epigenetic Modifications on Heterochromatin Factors2021

    • Author(s)
      Kamo, N.; Kujirai, T.; Kurumizaka, H.; Murakami, H.; Hayashi, G.; Okamoto, A.
    • Journal Title

      Chem. Sci.

      Volume: 12 Issue: 16 Pages: 5926-5937

    • DOI

      10.1039/d1sc00731a

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] cDNA TRAP display for rapid and stable in vitro selection of antibody-like proteins2021

    • Author(s)
      Kondo Taishi、Eguchi Minori、Kito Seita、Fujino Tomoshige、Hayashi Gosuke、Murakami Hiroshi
    • Journal Title

      Chemical Communications

      Volume: 57 Issue: 19 Pages: 2416-2419

    • DOI

      10.1039/d0cc07541h

    • NAID

      120007169556

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel Strategies of Peptide Ligation for Accelerating Chemical Protein Synthesis2020

    • Author(s)
      Hayashi Gosuke、Okamoto Akimitsu
    • Journal Title

      Journal of Synthetic Organic Chemistry, Japan

      Volume: 78 Issue: 2 Pages: 130-139

    • DOI

      10.5059/yukigoseikyokaishi.78.130

    • NAID

      130007795912

    • ISSN
      0037-9980, 1883-6526
    • Year and Date
      2020-02-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acetylation-modulated communication between the H3 N-terminal tail domain and the intrinsically disordered H1 C-terminal domain2020

    • Author(s)
      Hao, F; Murphy, K. J.; Kujirai, T.; Kamo, N.; Kato, J.; Koyama, M.; Okamato, A.; Hayashi, G.; Kurumizaka, H.; Hayes, J. J.
    • Journal Title

      Nucleic Acids Res.

      Volume: 48 Issue: 20 Pages: 11510-11520

    • DOI

      10.1093/nar/gkaa949

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] L-DNA-tagged fluorescence in situ hybridization for highly sensitive imaging of RNAs in single cells2020

    • Author(s)
      Ogata, M.; Hayashi, G.; Ichiu, A.; Okamoto, A.
    • Journal Title

      Org. Biomol. Chem.

      Volume: 18 Issue: 40 Pages: 8084-8088

    • DOI

      10.1039/d0ob01635g

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antibody-like proteins that capture and neutralize SARS-CoV-22020

    • Author(s)
      Kondo T.、Iwatani Y.、Matsuoka K.、Fujino T.、Umemoto S.、Yokomaku Y.、Ishizaki K.、Kito S.、Sezaki T.、Hayashi G.、Murakami H.
    • Journal Title

      Science Advances

      Volume: 6 Issue: 42 Pages: 3916-3916

    • DOI

      10.1126/sciadv.abd3916

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fmoc-Compatible and C-terminal-Sequence-Independent Peptide Alkyl Thioester Formation Using Cysteinylprolyl Imide2020

    • Author(s)
      Nakatsu, K.; Yanase, M.; Hayashi, G.; Okamoto, A.
    • Journal Title

      Org. Lett.

      Volume: 22 Issue: 12 Pages: 4670-4674

    • DOI

      10.1021/acs.orglett.0c01450

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Toolbox for chemically synthesized histone proteins2020

    • Author(s)
      Nakatsu, K.; Hayashi, G.; Okamoto, A.
    • Journal Title

      Curr. Opin. Chem. Biol.

      Volume: 58 Pages: 10-19

    • DOI

      10.1016/j.cbpa.2020.04.016

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] タンパク質化学合成を活用した翻訳後修飾研究2020

    • Author(s)
      林 剛介
    • Journal Title

      Farumashia

      Volume: 56 Issue: 1 Pages: 46-50

    • DOI

      10.14894/faruawpsj.56.1_46

    • NAID

      130007779027

    • ISSN
      0014-8601, 2189-7026
    • Related Report
      2019 Research-status Report
  • [Journal Article] Cysteinylprolyl imide (CPI) peptide: a highly reactive and easily accessible crypto-thioester for chemical protein synthesis2019

    • Author(s)
      Yanase Masafumi、Nakatsu Koki、Cardos Charlane Joy、Konda Yoshiki、Hayashi Gosuke、Okamoto Akimitsu
    • Journal Title

      Chemical Science

      Volume: 10 Issue: 23 Pages: 5967-5975

    • DOI

      10.1039/c9sc00646j

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Simultaneous and Traceless Ligation of Peptide Fragments on DNA Scaffold.2019

    • Author(s)
      Hayashi G, Yanase M, Nakatsuka Y, Okamoto A.
    • Journal Title

      Biomaclomolecules

      Volume: 20 Issue: 3 Pages: 1246-1253

    • DOI

      10.1021/acs.biomac.8b01655

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 修飾ヒストンの効率的化学合成法とヒストン動態解析2021

    • Author(s)
      林剛介
    • Organizer
      第14回日本エピジェネティクス研究会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] タンパク質化学合成技術を駆使した修飾タンパク質の創製と生化学研究への展開2020

    • Author(s)
      林剛介
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Challenges and prospects in chemoselective ligations: from protein synthesis to site-specific conjugation2020

    • Author(s)
      Gosuke Hayashi
    • Organizer
      LE STUDIUM CONFERENCES
    • Related Report
      2019 Research-status Report
  • [Presentation] Novel Peptide Ligation Strategies for Chemical Protein Synthesis2020

    • Author(s)
      Gosuke Hayashi
    • Organizer
      Seminar at University of Paris
    • Related Report
      2019 Research-status Report
  • [Presentation] Chemical Protein Synthesis with Novel Ligation Strategies2020

    • Author(s)
      Gosuke Hayashi
    • Organizer
      Seminar at CBM, CNRS Orleans Campus
    • Related Report
      2019 Research-status Report
  • [Presentation] 修飾タンパク質作製を可能にする最先端技術 ~生合成 vs 化学合成~2020

    • Author(s)
      林 剛介
    • Organizer
      第568回東北大学薬学研究科セミナー
    • Related Report
      2019 Research-status Report
  • [Presentation] Novel technologies for studying chromatin modifications2019

    • Author(s)
      Gosuke Hayashi
    • Organizer
      42nd MBSJ
    • Related Report
      2019 Research-status Report
  • [Presentation] エピジェネティクス研究とタンパク質化学合成2019

    • Author(s)
      林剛介
    • Organizer
      大阪大学蛋白質研究所セミナー
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] One-pot Sequential or Simultaneous Ligation of Multiple Peptide Fragments for Facilitating Chemical Protein Synthesis2018

    • Author(s)
      Gosuke Hayashi
    • Organizer
      ICPAC Langkawi2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] One-pot Multiple Peptide Ligation Strategies Harnessing Palladium Complex or DNA Scaffold2018

    • Author(s)
      Gosuke Hayashi, Naomi Kamo, Masafumi Yanase, and Akimitsu Okamoto
    • Organizer
      International Peptide Symposium 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] DNA Scaffold-mediated Peptide Ligation2018

    • Author(s)
      Gosuke Hayashi, Masafumi Yanase, Yoshiki Konda, Yu Nakatsuka and Akimitsu Okamoto
    • Organizer
      ISNAC2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 効率的タンパク質合成を指向した ペプチド連結法の開発2018

    • Author(s)
      林剛介、梁瀬将史、加茂直己、岡本晃充
    • Organizer
      第13回ケミカルバイオロジー学会
    • Related Report
      2018 Research-status Report
  • [Presentation] タンパク質化学合成を加速する ペプチドライゲーション戦略2018

    • Author(s)
      林剛介、梁瀬将史、加茂直己、誉田祥己、岡本晃充
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] アミノ酸の精密重合体であるタンパク質の化学的全合成とその効率化2018

    • Author(s)
      林剛介
    • Organizer
      第165回東海高分子研究会講演会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] 生体分子反応を制御する 化学的手法による機構と反応場の解明 「エピジェネティック修飾の謎を解き 明かす核酸およびタンパク質化学」2020

    • Author(s)
      林剛介、岡本晃充
    • Total Pages
      193
    • Publisher
      化学同人
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] フィブロネクチンIII型ドメイン骨格を含むポリペプチド2020

    • Inventor(s)
      村上裕、都築成晃、近藤大志、林剛介、藤野公茂、築地真也、吉井達之
    • Industrial Property Rights Holder
      村上裕、都築成晃、近藤大志、林剛介、藤野公茂、築地真也、吉井達之
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
  • [Patent(Industrial Property Rights)] 63.SARS-CoV-2 Binding Molecule2020

    • Inventor(s)
      村上裕、近藤大志、藤野公茂、林剛介、梅本駿、岩谷靖雅
    • Industrial Property Rights Holder
      村上裕、近藤大志、藤野公茂、林剛介、梅本駿、岩谷靖雅
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas

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Published: 2018-04-23   Modified: 2023-12-25  

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