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Establishment of artificial ligands technology for peptide hormone receptors with functional mutations

Research Project

Project/Area Number 16K08544
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionKanazawa University

Principal Investigator

Sakai Kastuya  金沢大学, がん進展制御研究所, 助教 (10523318)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords受容体 / リガンド / 環状ペプチド / ペプチド / 人工リガンド
Outline of Final Research Achievements

Artificial ligands for growth factor receptors are clinically applicable. We here tried identification of artificial ligands for insulin receptor (IR) using macrocyclic peptide screening, and characterized MET-agonist macrocyclic peptides to establish artificial ligand technology based on macrocyclic peptide. Expression and purification of IR protein with its kinase activity was difficult. Now, purification of IR in nanodiscs is being investigated. We have proved that 1) artificial ligands based on macrocyclic peptide are able to have similar activity compared to natural ligands, 2) partial agonists based on macrocyclic peptide are able to induced biased or selective cellular responses compared to natural ligands, and 3) macrocyclic peptides interact with thier target protein in an unique manner. These results illustrate potential of artificial ligands based on macrocyclic peptides.

Academic Significance and Societal Importance of the Research Achievements

ペプチド・タンパク質ホルモンや/増殖因子は細胞膜受容体を介して生理活性を発揮する。本課題により低分子人工ペプチド性リガンドを着実に創製できる技術を実証したこと、これらの技術の基盤となる知見を得られたことは、医薬品として際立った薬効をもつ複数の低分子生理活性医薬を創製する技術原理を確立することにつながる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (13 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 3 results) Book (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Macrocyclic peptide-based inhibition and imaging of hepatocyte growth factor2019

    • Author(s)
      Katsuya Sakai, Toby Passioura, Hiroki Sato, Kenichiro Ito, Hiroki Furuhashi, Masataka Umitsu, Junichi Takagi, Yukinari Kato, Hidefumi Mukai, Shota Warashina, Maki Zouda, Yasuyoshi Watanabe, Seiji Yano, Mikihiro Shibata, Hiroaki Suga, and Kunio Matsumoto
    • Journal Title

      Nature Chemical Biology

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellular signaling and gene expression profiles evoked by a bivalent macrocyclic peptide that serves as an artificial MET receptor agonist2018

    • Author(s)
      Miao Wenyu、Sakai Katsuya、Ozawa Naoya、Nishiuchi Takumi、Suzuki Yoshinori、Ito Kenichiro、Morioka Tomomi、Umitsu Masataka、Takagi Junichi、Suga Hiroaki、Matsumoto Kunio
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 16492-16492

    • DOI

      10.1038/s41598-018-34835-4

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MET Activation by a Macrocyclic Peptide Agonist that Couples to Biological Responses Differently from HGF in a Context-Dependent Manner.2018

    • Author(s)
      Miao W, Sakai K, Imamura R, Ito K, Suga H, Sakuma T, Yamamoto T, Matsumoto K.
    • Journal Title

      Int J Mol Sci.

      Volume: 19 Issue: 10 Pages: 3141-3141

    • DOI

      10.3390/ijms19103141

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Single-molecule nano-scale observation of growth factor and receptor2019

    • Author(s)
      Sakai Katsuya
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] PET imaging system reflecting activation status of HGF/Met signalling with macro-cyclic peptides.2018

    • Author(s)
      Sato H, Sakai K, Mukai H, Watanabe Y, Passioura T, Suga H, Matsumoto K.
    • Organizer
      The 1st NanoLSI International Symposium.
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 選択的生物活性をもつ環状ペプチドによるMET/HGF受容体アゴニストの創成2018

    • Author(s)
      Miao Wenyu、酒井克也、伊藤健一郎、菅裕明、松本邦夫
    • Organizer
      第91回日本生化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cellular Signaling and Gene Expression Profiles Evoked by Artificial MET/HGF Receptor-Agonist of Macrocyclic Peptide2017

    • Author(s)
      Wenyu Miao, Katsuya Sakai, Naoya Ozawa, Kenichiro Ito, Hiroaki Suga, Kunio Matsumoto
    • Organizer
      11th International Symposium of The Institute Network
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Activation and detection of Met/HGF receptor by cyclic peptide technology2017

    • Author(s)
      Wenyu Miao, Katsuya Sakai, Naoya Ozawa, Kenichiro Ito, Hiroaki Suga, Kunio Matsumoto
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Cellular Signaling and Gene Expression Profiles Evoked by Artificial MET/HGF Receptor-Agonist of Macrocyclic Peptide2017

    • Author(s)
      Wenyu Miao, Katsuya Sakai, Naoya Ozawa, Kenichiro Ito, Hiroaki Suga, Kunio Matsumoto
    • Organizer
      第90回 日本生化学会大会
    • Related Report
      2017 Research-status Report
  • [Book] ものづくり技術からみる再生医療ー細胞研究・創薬・治療ー2018

    • Author(s)
      酒井 克也、松本 邦夫
    • Total Pages
      282
    • Publisher
      シーエムシー出版
    • Related Report
      2018 Annual Research Report
  • [Book] ペプチド医薬品の スクリーニング・安定化・製剤化技術2017

    • Author(s)
      酒井克也ら 共著
    • Total Pages
      557
    • Publisher
      技術情報協会
    • Related Report
      2017 Research-status Report
  • [Book] 医療・診断をささえるペプチド科学2017

    • Author(s)
      松本邦夫 菅裕明 酒井克也ら 共著
    • Total Pages
      315
    • Publisher
      シーエムシー出版
    • ISBN
      9784781312675
    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 環状ペプチド2018

    • Inventor(s)
      酒井 克也
    • Industrial Property Rights Holder
      酒井 克也
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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