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Development of environment-responsive targeted molecules from fluorophore library via 2-step maturation

Research Project

Project/Area Number 17K05925
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bio-related chemistry
Research InstitutionThe University of Electro-Communications

Principal Investigator

Taki Masumi  電気通信大学, 大学院情報理工学研究科, 准教授 (70362952)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords蛍光センサー型分子 / 標的結合体 / 加水分解 / ダイナミックコンビナトリアルライブラリー / サイズ排除クロマトグラフィー / ヒト血清アルブミン / セレクション / シッフ塩基 / Keep-on型蛍光分子ライブラリー / ヒト血清アルブミン(HSA) / LC-MS/MS / コンビナトリアル合成 / ねじれ型分子内電荷移動 / スズキカップリング / ファージディスプレイ / 環境応答性蛍光分子 / バイオテクノロジー
Outline of Final Research Achievements

A low-molecular-weight pharmacophore, as a targeted fluoroprobe, was selected from a dynamic combinatorial library of Schiff bases by using size-exclusion chromatography. The identified pharmacophore retained its fluorescence when bound to the hydrophobic site of the target, whereas it lost because of hydrolysis when unbound. We defined it as keep-on type fluorescence probe because the fluorescent pharmacophore is only kept intact when bound to the target (Y. Tabuchi, M. Taki, Anal. Bioanal. Chem. 410, 6713 (2018)).

Academic Significance and Societal Importance of the Research Achievements

従来の環境応答性蛍光センサー型分子は、標的蛋白質に結合することで蛍光色が変わったり蛍光強度が上がったりする(Turn-onする)原理で作用していた。今回、センサー型分子に水分子と化学反応して蛍光を失うという性質を持たせ、標的蛋白質に結合しているときだけ水分子と反応せず蛍光性を保つ(Keep-onする)原理を着想した。本原理にて標的の蛍光検出を行うという発想はこれまでに無く、学術的に新しい。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Fluorescent “keep-on” type pharmacophore obtained from dynamic combinatorial library of Schiff bases2018

    • Author(s)
      Tabuchi Yudai、Taki Masumi
    • Journal Title

      Analytical and Bioanalytical Chemistry

      Volume: 410 Issue: 26 Pages: 6713-6717

    • DOI

      10.1007/s00216-018-1303-4

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Discovering protein-specific binders via tandem screening: combination of size exclusion chromatography and extended phage display2019

    • Author(s)
      Fumiko Hisamatsu, Masumi Taki
    • Organizer
      第56回ペプチド討論会(56JPS)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Fluorescent "keep-on" type pharmacophore obtained from dynamic combinatorial library of Schiff bases2019

    • Author(s)
      Yudai Tabuchi, Masumi Taki
    • Organizer
      International Symposium on Dyes & Pigments (Elsevier)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Turn-on / keep-on fluorescent molecules as targeted binders2019

    • Author(s)
      Masumi Taki
    • Organizer
      The third international workshop on symbiosis of biology and nanodevices (JSPS)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 加水分解型蛍光分子を用いた蛋白質検出法の開発2018

    • Author(s)
      田淵 雄大・谷田部 和貴・瀧 真清
    • Organizer
      日本化学会 第98春季年会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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