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Design principle for creating chemically synthesizable antibody mimetics composed of constrained target-binding peptides and natural scaffold peptides

Research Project

Project/Area Number 16K15141
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionTokyo Institute of Technology

Principal Investigator

KADONOSONO TETSUYA  東京工業大学, 生命理工学院, 助教 (10510282)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords中分子創薬 / 創薬デザイン技術 / タンパク質分子設計 / 抗体代替分子 / 標的結合小型タンパク質 / インシリコスクリーニング / HTS / HER2 / 足場天然ペプチド / 構造ゆらぎ / イン・シリコ・スクリーニング / HER2結合ペプチド / 医薬分子設計 / 標的結合ペプチド
Outline of Final Research Achievements

Target-binding peptides which have a small molecular weight and capable of chemical synthesis are expected as an alternative drug to antibodies. However, target-binding peptides often have weak affinity and no examples have been put into clinical use so far. Therefore, in this study, I aimed to establish the design principle of chemically synthesizable antibody mimetics composed of constrained target-binding peptides and natural scaffold peptides and obtained following results; A) establishment of the generation theory of high performance antibody mimetics by controlling "structural fluctuation", B) establishment of search method of natural peptide usable as a scaffold peptide, C) establishment of the control method of peptide fluctuation by using natural scaffold peptides. Based on this principle, it is expected that it will be able to provide cheap antibody alternatives with binding capacity equivalent to that of antibodies.

Report

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

    (24 results)

All 2017 2016

All Presentation (22 results) (of which Invited: 3 results) Book (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Presentation] 構造ゆらぎ制御による高親和性PD-1結合ペプチド医薬の創製戦略2017

    • Author(s)
      門之園 哲哉
    • Organizer
      ペプチド医薬品における活性,安定性,吸収性改善
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Development of high-affinity tumor imaging probes based on constrained target-binding peptides2017

    • Author(s)
      Wanaporn Yimchuen, Tetsuya Kadonosono, Tadaomi Furuta, Takahiro Kuchimaru, Shinae Kondoh
    • Organizer
      第12回日本分子イメージング学会総会・学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトフィブロネクチンIII型ドメインを利用した抗HER2抗体代替分子の開発2017

    • Author(s)
      太田 優美, 門之園 哲哉, 口丸 高弘, 近藤 科江
    • Organizer
      第21回日本がん分子標的治療学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 小型抗体代替分子の創出に向けた低分子量足場タンパク質の探索2017

    • Author(s)
      門之園 哲哉, 太田 優美, 口丸 高弘, 近藤 科江
    • Organizer
      第21回日本がん分子標的治療学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 構造ゆらぎ制御による小型抗体代替分子の創出2017

    • Author(s)
      門之園 哲哉
    • Organizer
      第3回蛋白質工学研究会ワークショップ
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 構造ゆらぎ抑制による抗HER2抗体代替分子の創製2017

    • Author(s)
      太田 優美, 門之園 哲哉, 口丸 高弘, 瀧 真清, 伊東 祐二, 近藤 科江
    • Organizer
      第49回若手ペプチド夏の勉強会
    • Related Report
      2017 Annual Research Report
  • [Presentation] A screening system for identifying biocompatible low-molecular-mass scaffold proteins to develop small antibody mimetics2017

    • Author(s)
      Tetsuya Kadonosono, Yumi Ota, Wanaporn Yimchuen, Takahiro Kuchimaru, Shinae Kondoh
    • Organizer
      The 76th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of high affinity anti-HER2 antibody mimetics by use of human fibronectin type III domain2017

    • Author(s)
      Yumi Ota, Tetsuya Kadonosono, Wanaporn Yimchuen, Takahiro Kuchimaru, Shinae Kondoh
    • Organizer
      The 76th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腫瘍悪性化促進因子の活性を中和する抗体代替分子の創製2017

    • Author(s)
      門之園 哲哉, Kyra See, 勝見 茉莉奈, 太田 優美, Wanaporn Yimchuen, 相田 一希, 口丸 高弘, 近藤 科江
    • Organizer
      第15回がんとハイポキシア研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of anti-HER2 antibody mimetics with structurally constrained CDR peptides2017

    • Author(s)
      Wanaporn Yimchuen, Tetsuya Kadonosono, Kyra See, Tadaomi Furuta, Takahiro Kuchimaru, Shinae Kondoh
    • Organizer
      第54回ペプチド討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of HER2-targeting small protein harboring a structurally constrained peptide2017

    • Author(s)
      Yumi Ota, Tetsuya Kadonosono, Takahiro Kuchimaru, Masumi Taki, Yuji Ito, Shinae Kondoh
    • Organizer
      第54回ペプチド討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Creation of high performance antibody drug altenatives harvoring constrained CDR peptides2017

    • Author(s)
      Tetsuya Kadonosono, Yumi Ota, Wanaporn Yimchuen, Kyra See, Tadaomi Furuta, Takahiro Kuchimaru, Shinae Kondoh
    • Organizer
      第54回ペプチド討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒトフィブロネクチンIII型ドメインを足場とする小型HER2結合分子の創製2017

    • Author(s)
      太田 優美, 門之園 哲哉, 口丸 高弘, 瀧 真清, 伊東 祐二, 近藤 科江
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抗体CDRペプチドの構造ゆらぎ制御による小型抗体代替分子の創製2017

    • Author(s)
      門之園 哲哉, Wanaporn Yimchuen, Kyra See, 太田 優美, 口丸 高弘, 近藤 科江
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抗体代替中分子の半合理的デザイン2017

    • Author(s)
      門之園 哲哉
    • Organizer
      第6回蛋白質間相互作用研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 構造ゆらぎ制御による抗体代替分子の創製2017

    • Author(s)
      門之園 哲哉
    • Organizer
      第2回マイクロプロテイン研究会
    • Place of Presentation
      東京工業大学すずかけ台キャンパス(神奈川)
    • Related Report
      2016 Research-status Report
  • [Presentation] 構造ゆらぎの抑制による抗体代替分子の創製2017

    • Author(s)
      門之園 哲哉
    • Organizer
      第5回蛋白質間相互作用研究会
    • Place of Presentation
      御殿場時之栖(静岡)
    • Related Report
      2016 Research-status Report
  • [Presentation] 抗体由来標的結合ペプチドの「構造ゆらぎ」抑制による高性能な抗体代替分子の開発2016

    • Author(s)
      門之園 哲哉, 口丸 高弘, 近藤 科江
    • Organizer
      第20回日本がん分子標的治療学会学術集会
    • Place of Presentation
      別府国際コンベンションセンター(大分)
    • Related Report
      2016 Research-status Report
  • [Presentation] 化学合成可能な高性能抗体代替分子の開発技術2016

    • Author(s)
      門之園 哲哉
    • Organizer
      技術情報協会セミナー「ペプチド医薬品の市場予測・事業化戦略と製剤化技術の開発」
    • Place of Presentation
      技術情報協会セミナールーム(東京)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 標的結合ペプチドのゆらぎ制御による抗体代替分子の創製法2016

    • Author(s)
      門之園 哲哉、Wanaporn Yimchuen、塩澤 唯、北澤 舞花、太田 優美、口丸 高弘、近藤 科江
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川)
    • Related Report
      2016 Research-status Report
  • [Presentation] A protein-engineering method for identifying a scaffold making peptides structurally constrained in order to develop high-affinity antibody mimetics2016

    • Author(s)
      Tetsuya Kadonosono, Wanaporn Yimchuen, Tadashi Shiozawa, Maika Kitazawa, Yumi Ota, Takahiro Kuchimaru, and Shinae Kondoh
    • Organizer
      第53回ペプチド討論会
    • Place of Presentation
      京都テルサ(京都)
    • Related Report
      2016 Research-status Report
  • [Presentation] 「構造ゆらぎ」制御による高性能な抗体医薬品代替分子の創製2016

    • Author(s)
      門之園 哲哉, Wanaporn Yimchuen, 塩澤 唯, 北澤 舞花, 太田 優美, 口丸 高弘, 近藤 科江
    • Organizer
      第5回 次世代がん治療推進専門家養成プランシンポジウム
    • Place of Presentation
      東京医科歯科大学湯島キャンパス(東京)
    • Related Report
      2016 Research-status Report
  • [Book] ペプチド医薬品開発のためのスクリーニング・安定化・製剤化技術2017

    • Author(s)
      門之園 哲哉
    • Total Pages
      557
    • Publisher
      技術情報協会
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 標的結合ペプチドの安定化方法2016

    • Inventor(s)
      門之園哲哉、近藤科江
    • Industrial Property Rights Holder
      門之園哲哉、近藤科江
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-12-28
    • Related Report
      2016 Research-status Report
    • Overseas

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

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