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Peptide ligand screening of transthyretin protein-protein interaction inhibitor using phage display system

Research Project

Project/Area Number 16K18875
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionKumamoto University

Principal Investigator

SATO Takashi  熊本大学, 大学院生命科学研究部(薬), 助教 (70555755)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsトランスサイレチン / 家族性アミロイドポリニューロパチー / ファージディスプレイ / タンパク質間相互作用 / 環状ペプチド / ペプチド / アミロイドーシス
Outline of Final Research Achievements

Familial Amyloidotic Polyneuropathy (FAP) is one of the systemic amyloidosis, which is caused by a point mutation in transthyretin (TTR). Because mutant TTR forms amyloid fibrils after secretion from the cells, we believed that secretory inhibition of mutant TTR followed by their intracellular degradation could be a potential drug target for FAP. We previously demonstrated that inhibition of TTR tetramerization in the endoplasmic reticulum blocks secretion of mutant TTR. In this study, we aimed to determine peptides that could inhibit TTR tetramerization using the phage display system. Here, we identified three cyclic peptides that bind to TTR. Two of the three peptides could destabilize conformations of tetrameric and monomeric TTRs.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (5 results) Remarks (1 results)

  • [Journal Article] Production of Single-Chain Fv Antibodies Specific for GA-Pyridine, an Advanced Glycation End-Product (AGE), with Reduced Inter-Domain Motion2017

    • Author(s)
      Fukuda N、Noi K、Weng L、Kobashigawa Y、Miyazaki H、Wakeyama Y、Takaki M、Nakahara Y、Tatsuno Y、Uchida-Kamekura M、Suwa Y、Sato T、Ichikawa-Tomikawa N、Nomizu M、Fujiwara Y、Ohsaka F、Saitoh T、Maenaka K、Kumeta H、Shinya S、Kojima C、Ogura T、Morioka H
    • Journal Title

      Molecules

      Volume: 22 Issue: 10 Pages: 1695-1695

    • DOI

      10.3390/molecules22101695

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm.2017

    • Author(s)
      Koga T, Shiraki N, Yano S, Suico MA, Morino-Koga S, Sato T, Shuto T, Kume S, Kai H
    • Journal Title

      BMC Biotechnology

      Volume: 17 Issue: 1 Pages: 14-14

    • DOI

      10.1186/s12896-017-0331-z

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] トランスサイレチンのタンパク質間相互作用を標的とした遺伝性ATTR アミロイドーシスの創薬研究2018

    • Author(s)
      佐藤 卓史、小橋川 敬博、甲斐 広文、森岡 弘志
    • Organizer
      第5回生命分子科学研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] トランスサイレチン単量体の動的な構造平衡状態の解析2018

    • Author(s)
      河野 慎吾、小橋川 敬博、甲斐 広文、森岡 弘志、佐藤 卓史
    • Organizer
      第5回生命分子科学研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] トランスサイレチンの品質管理における小胞体分子シャペロンの基質認識機構の解明2018

    • Author(s)
      稲田 祐貴、河野 慎吾、小橋川 敬博、森岡 弘志、佐藤 卓史
    • Organizer
      第5回生命分子科学研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] トランスサイレチンのタンパク質間相互作用を標的とした家族性アミロイドポリニューロパチーの創薬研究2017

    • Author(s)
      佐藤卓史、河野慎吾、稲田祐貴、小橋川敬博、甲斐広文、森岡弘志
    • Organizer
      第12日本ケミカルバイオロジー学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] トランスサイレチン単量体の構造安定化を標的とする創薬スクリーニング系の構築2017

    • Author(s)
      河野慎吾、稲田裕貴、小橋川敬博、甲斐広文、森岡弘志、佐藤卓史
    • Organizer
      第12回日本ケミカルバイオロジー学会年会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 熊本大学大学院生命科学研究部生命分析化学分野ホームページ

    • URL

      http://seimeibunseki.org

    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2019-03-29  

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