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Development of novel cyclic peptides that detect molecular states of collagen in vitro and in vivo

Research Project

Project/Area Number 17K19502
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Pharmaceutical Sciences and related fields
Research InstitutionWaseda University

Principal Investigator

KOIDE Takaki  早稲田大学, 理工学術院, 教授 (70322253)

Co-Investigator(Kenkyū-buntansha) 木村 寛之  京都薬科大学, 薬学部, 准教授 (50437240)
増田 亮  早稲田大学, 理工学術院, 次席研究員(研究院講師) (90632159)
Research Collaborator TAKITA Koh K.  
FUJII Kazunori K.  
Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywordsコラーゲン / ペプチド / イメージング / 薬物送達 / がん / 3重らせん
Outline of Final Research Achievements

It is proposed that tissues surrounding malignant tumors are rich in (partially) denatured collagen. Thus, development of a probe that detects denatured collagen with high efficiency has been expected. In this study, based on the design of previously published peptides capable of hybridizing with an unfolded triple helix, we have developed peptides that can detect it with higher sensitivity. The peptides are cyclic dimers of peptides with collagen-like sequences. One of the cyclic peptides showed two-orders of magnitude higher affinity to denatured collagen than conventional single chain counterpart. The peptide was shown to be applicable to sensitive detection of collagen in vitro. In addition, it enabled in vivo fluorescent imaging of malignant tumors in mouse models.

Academic Significance and Societal Importance of the Research Achievements

がん、骨・軟骨疾患、線維化、炎症性疾患などでコラーゲン3重らせんが変性していることが予想されており、それを検出するプローブの開発が求められていた。これまでに1本鎖のコラーゲン様ペプチドがこの目的で試されてきたが、本研究においては、分子設計の改変により約2オーダーの結合能の改善を達成できた。これにより、培養細胞レベルから生体のイメージングに至る広範囲な実験系において、緩んだ3重らせんを検出、定量、可視化することが可能となった。この成果は、基礎研究から診断薬・治療薬開発を目指した応用研究まで幅広い研究領域にひとつの新たなツールを付け加えた。

Report

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

    (10 results)

All 2018 2017 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Cyclic Peptides for Efficient Detection of Collagen2018

    • Author(s)
      Takita Koh K.、Fujii Kazunori K.、Kadonosono Tetsuya、Masuda Ryo、Koide Takaki
    • Journal Title

      ChemBioChem

      Volume: 19 Issue: 15 Pages: 1613-1617

    • DOI

      10.1002/cbic.201800166

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] Targeting Unfolded Collagen by Cyclic Collagen-Mimetic Peptides2018

    • Author(s)
      Takaki Koide, Koh K. Takita, Kazunori K. Fujii, Ryo Masuda, Tetsuya Kadonosono, Hiroyuki Kimura
    • Organizer
      10th International Peptide Sym
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Development of a collagen-detecting peptide and its application in vivo.2018

    • Author(s)
      K.K. Takita, K.K. Fujii, H. Kimura, T. Koide
    • Organizer
      第50回 日本結合組織学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] コラーゲン3重らせんにインスパイアされたペプチド創薬2018

    • Author(s)
      小出隆規
    • Organizer
      日本薬学会第138年回
    • Related Report
      2017 Research-status Report
  • [Presentation] Cyclic peptides for efficient detection of collagen2017

    • Author(s)
      Koh K. Takita, Kazunori K. Fujii, Takaki Koide
    • Organizer
      第54回ペプチド討論会
    • Related Report
      2017 Research-status Report
  • [Presentation] Seamless cyclization of collagen-like peptides with Gly-X-Y-repeating sequences2017

    • Author(s)
      Kazuki C. Kuroda, Fumiko Hisamatsu, Takaki Koide
    • Organizer
      第54回ペプチド討論会
    • Related Report
      2017 Research-status Report
  • [Remarks] 小出研究室

    • URL

      http://www.chem.waseda.ac.jp/koide/

    • Related Report
      2018 Annual Research Report
  • [Remarks]

    • URL

      http://www.chem.waseda.ac.jp/koide/

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] コラーゲンへの結合活性を有する環状ペプチド2018

    • Inventor(s)
      小出隆規、瀧田講、平和馬
    • Industrial Property Rights Holder
      小出隆規、瀧田講、平和馬
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] コラーゲンへの結合活性を有する環状ペプチド2017

    • Inventor(s)
      小出隆規、瀧田講、平和馬
    • Industrial Property Rights Holder
      小出隆規、瀧田講、平和馬
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-166687
    • Filing Date
      2017
    • Related Report
      2017 Research-status Report

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Published: 2017-07-21   Modified: 2020-03-30  

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