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Development of macrocylclic peptide drug that targets membrane proteins using cultivated human cell lines

Research Project

Project/Area Number 24681047
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Chemical biology
Research InstitutionThe University of Tokyo

Principal Investigator

KATOH Takayuki  東京大学, 理学(系)研究科(研究院), 助教 (90567760)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥26,910,000 (Direct Cost: ¥20,700,000、Indirect Cost: ¥6,210,000)
Fiscal Year 2014: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2013: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2012: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Keywords膜タンパク質 / ペプチド医薬 / RaPIDディスプレイ / 翻訳 / 遺伝暗号リプログラミング / アゴニスト / 特殊環状ペプチド / 阻害剤 / RaPID display / 医薬品探索 / 分子標的医薬 / 特殊ペプチド / GPCR
Outline of Final Research Achievements

In this research project, we developed a new method for screening non-standard macrocyclic peptide drugs that target cell-surface molecules such as membrane proteins. Normally, target molecules need to be immobilized on magnetic beads for applying in-vitro display method combined with random peptide library. However, immobilization of membrane proteins is generally difficult because isolation and solubilization of such proteins are impossible in many cases. Therefore, in this project, we developed a new in-vitro display method that utilizes cultured cells and/or baculovirus expressing membrane proteins on their surface instead of purified proteins immobilized on beads. By using this method, we could successfully obtain macrocyclic peptides that target CD20, IL28RA, Claudin-1 and 4.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (8 results)

All 2014 2013 2012

All Journal Article (5 results) (of which Peer Reviewed: 4 results) Presentation (2 results) (of which Invited: 1 results) Book (1 results)

  • [Journal Article] Selection-Based Discovery of Druglike Macrocyclic Peptides.2014

    • Author(s)
      Passioura T, Katoh T, Goto Y, Suga H.
    • Journal Title

      Annu. Rev. Biochem.

      Volume: 未定

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A macrocyclic peptide that serves as a cocrystallization ligand and inhibits the function of a MATE family transporte2013

    • Author(s)
      C・J・ Hipolito, Y・Tanaka, T・ Katoh, O・ Nureki, H・ Suga
    • Journal Title

      Molecules

      Volume: 18 Issue: 9 Pages: 10514-30

    • DOI

      10.3390/molecules180910514

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the drug extrusion mechanism by a MATE multidrug transporter2013

    • Author(s)
      Y・ Tanaka, C・J・ Hipolito, A・D・ Maturana, K・ Ito, T・ Kuroda, T・ Higuchi, T・ Katoh, H・E・ Kato, M・ Hattori, K・ Kumazaki, T・ Tsukazaki, R・ Ishitani, H・ Suga, O・ Nureki
    • Journal Title

      Nature

      Volume: 496 Issue: 7444 Pages: 247-51

    • DOI

      10.1038/nature12014

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RNAワールドの実験的検証2013

    • Author(s)
      岩根由彦、高辻諒、加藤敬行、菅裕明
    • Journal Title

      進化分子工学

      Volume: なし Pages: 49-60

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Selective thioether macrocyclization of peptides having the N-terminal 2-chloroacetyl group and competing two or three cysteine residues in translation2012

    • Author(s)
      Kazuhiro Iwasaki, Yuki Goto, Takayuki Katoh, Hiroaki Suga
    • Journal Title

      Org.Biomol.Chem.

      Volume: 10 Issue: 30 Pages: 5783-5786

    • DOI

      10.1039/c2ob25306b

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 細胞を用いたRaPIDシステムによるIL28RA結合ペプチドの探索2014

    • Author(s)
      石田啓、平田雄一、加藤敬行、小原道法、菅裕明
    • Organizer
      第46回 若手ペプチド夏の勉強会
    • Place of Presentation
      京都府立青少年海洋センター(京都府宮津市)
    • Year and Date
      2014-08-03 – 2014-08-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 特殊環状ペプチド創薬2013

    • Author(s)
      加藤敬行
    • Organizer
      日本生化学会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] 生命システム工学2012

    • Author(s)
      加藤敬行、後藤佑樹、菅裕明, 他
    • Total Pages
      213
    • Publisher
      化学同人
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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