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Development of fluorescent probes highly sensitive to membrane potential and their design principles

Research Project

Project/Area Number 19K05729
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 37030:Chemical biology-related
Research InstitutionUtsunomiya University

Principal Investigator

Oba Toru  宇都宮大学, 工学部, 教授 (30291793)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords蛍光プローブ / 膜電位 / 神経細胞 / 超分子 / ケミカルバイオロジー / イメージング / エレクトロクロミズム
Outline of Research at the Start

精神疾患や認知症、神経疾患の克服は,我が国の重要取り組み事項とされている。神経細胞の診断技術(イメージング)は脳研究の重要なツールであるが,広範囲の微弱な神経活動(活動電位)を高感度で可能にする蛍光プローブはまだない。そこで本研究では,広範囲の神経細胞の活動電位を,高感度でイメージングできる膜電位感受性蛍光色素を開発するとともに,その分子設計指針の確立を目的とする。

Outline of Final Research Achievements

To overcome psychiatric disorder or dementia, this study aims at developing highly sensitive voltage-sensitive fluorescent dyes for study and diagnosis of nerve cell networks. We found a new method to evaluate voltage-sensitivity of the dyes by utilizing micellar dipole potential. Exploration of the voltage-detecting part indicated that a quinoline-based dye with a dimethylaminophenylethynyl moiety as a promising structure. We successfully synthesized a new bodipy dye with this voltage-detecting part, and confirmed their voltage-sensitivity. We also obtained boron-containing amino-acid analogs that can be used to link the dyes to lipids or proteins.

Academic Significance and Societal Importance of the Research Achievements

①高感度な膜電位感受性蛍光色素の新たな分子設計指針を得ることができた。すなわち、電位検出部位と蛍光発色団を分離し、電子移動消光などにより速やかに励起エネルギーを散逸させることによって、感度と光安定性とを両立させることである。②この色素は神経細胞の診断の他にも、心筋のイオンチャネル標的薬のスクリーニングや、ミトコンドリア病の診断、ウイルスの侵入や放出に伴う細胞膜の変化の検出にも応用を期待できる。③新たに合成したホウ素化合物は、抗がん剤原料などにも応用できるだろう。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (25 results)

All 2022 2021 2020 2019 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (17 results) Remarks (2 results)

  • [Journal Article] Amine-Selective Reaction of 2H-Azirine for Synthesis of Peptidomimetics2022

    • Author(s)
      Hiroto Takahashi, Makoto Roppongi, Shingo Tamesue, Toru Oba
    • Journal Title

      Peptide Science 2021

      Volume: - Pages: 137-138

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of quinolyl-pyrrole derivatives as novel environment-sensitive fluorescent probes2019

    • Author(s)
      Shinotsuka Ryo、Oba Toru、Mitome Takahiro、Masuya Takuto、Ito Satoshi、Murakami Yukie、Kagenishi Tomoko、Kodama Yutaka、Matsuda Masaru、Yoshida Takashi、Wakamori Minoru、Ohkura Masamichi、Nakai Junichi
    • Journal Title

      Journal of Photochemistry and Photobiology A: Chemistry

      Volume: 382 Pages: 111900-111900

    • DOI

      10.1016/j.jphotochem.2019.111900

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of green fluorescent protein chromophore analogues for interdisciplinary learning for high school students2019

    • Author(s)
      Shiho Numanoi, Makiko Hashimoto, Sonoko Hashimoto, Katsunori Kazawa, Ryo Sakaguchi, Kota Miyata, Rino Iwakami, Takahiro Mitome, Shintaro Anju, Ryo Shinotsuka, Toru Oba
    • Journal Title

      J. Chem. Educ.

      Volume: 96 Issue: 3 Pages: 503-507

    • DOI

      10.1021/acs.jchemed.8b00443

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of p-borono-L-phenylalanine (BPA)-like aza-amino acids2019

    • Author(s)
      Kota Miyata, Airi Narita, Ryota Fujisawa, Makoto Roppongi, Shingo Tamesue, Satoshi Ito, and Toru Oba
    • Journal Title

      Peptide Science 2019

      Pages: 41-42

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] 2H-azirines as novel precursors od peptidemimetics2019

    • Author(s)
      Toru Oba, Yuka Yoshizawa, Shintaro Anju, Hiroto Takahashi, Kota Miyata, Satoshi Ito, and Makoto Roppongi
    • Journal Title

      Peptide Science 2019

      Pages: 91-92

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Supramolecules of peptidemimetics with multiple-boronates2019

    • Author(s)
      Kota Miyata, Ryota Fujisawa, Airi Narita, Makoto Roppongi, Shingo Tamesue, Satoshi Ito, and Toru Oba
    • Journal Title

      Peptide Science 2019

      Pages: 87-88

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] キノリン型分子ワイヤーの電位応答性とその蛍光プローブへの応用2022

    • Author(s)
      河原田悠・六本木 誠・為末慎吾・大庭 亨
    • Organizer
      日本化学会第102回春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] azaBPAを含む新規なGrb2阻害剤の開発2022

    • Author(s)
      押野 優大・六本木 誠・為末 真吾・大庭 亨
    • Organizer
      日本化学会第102回春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] azaBPAを含むペプチドミメティクスの合成2022

    • Author(s)
      及川 大翔・六本木 誠・為末 真吾・大庭 亨
    • Organizer
      日本化学会第102回春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 環境応答性プローブへの応用を目指した新規フェナジン類の合成2022

    • Author(s)
      千葉 拓海・六本木 誠・為末 真吾・大庭 亨
    • Organizer
      日本化学会第102回春季年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] キノリニウム型蛍光色素の合成および環境応答性2021

    • Author(s)
      大庭 亨、菅原 亜季、六本木 誠、為末 真吾
    • Organizer
      第15回バイオ関連化学シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] Amine-Selective Reaction of 2H-Azirine for Synthesis of Peptidomimetics2021

    • Author(s)
      Hiroto Takahashi, Makoto Roppongi, Shingo Tamesue, Toru Oba
    • Organizer
      第58回ペプチド討論会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 環境応答性蛍光プローブへの応用を志向した(2-キノリル)アリール類の合成2021

    • Author(s)
      大庭 亨、加嶋 啓史、市川 晋太郎、伊藤 智志、為末 真吾、児玉 豊
    • Organizer
      日本化学会第101回春季年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Synthesis of boronated azapeptides and their derivatives2020

    • Author(s)
      Ryota Fujisawa, Kota Miyata, Airi Narita, Makoto Roppongi, Shingo Tamesue, Satoshi Ito, Toru Oba
    • Organizer
      第57回ペプチド討論会,
    • Related Report
      2020 Research-status Report
  • [Presentation] Synthesis of boron-containing azirine and its derivatives2020

    • Author(s)
      Toru Oba, Hiroto Takahashi, Yuka Yoshizawa, Makoto Roppongi, Shingo Tamesue, Satoshi Ito
    • Organizer
      第57回ペプチド討論会,
    • Related Report
      2020 Research-status Report
  • [Presentation] キノリルフェノチアジンを骨格とする環境応答性蛍光プローブの開発2019

    • Author(s)
      大庭 亨,棚沢公貴,伊藤智志,六本木 誠,為末真吾
    • Organizer
      第13回バイオ関連化学シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] Synthesis and structural characteristics of boron-containing azapeptides2019

    • Author(s)
      Kota Miyata, Airi Narita, Ryota Fujisawa, Makoto Roppongi, Shingo Tamesue, Satoshi Ito, and Toru Oba
    • Organizer
      第56回ペプチド討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] Synthesis of p-borono-L-phenylalanine (BPA)-like aza-amino acids2019

    • Author(s)
      Kota Miyata, Airi Narita, Ryota Fujisawa, Makoto Roppongi, Shingo Tamesue, Satoshi Ito, and Toru Oba
    • Organizer
      第56回ペプチド討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] 2H-azirines as novel precursors of peptidemimetics2019

    • Author(s)
      Toru Oba, Yuka Yoshizawa, Shintaro Anju, Hiroto Takahashi, Kota Miyata, Satoshi Ito, and Makoto Roppongi
    • Organizer
      第56回ペプチド討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] Supramolecules of peptidemimetics with multiple-boronates2019

    • Author(s)
      Kota Miyata, Ryota Fujisawa, Airi Narita, Makoto Roppongi, Shingo Tamesue, Satoshi Ito, and Toru Oba
    • Organizer
      第56回ペプチド討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] Synthesis and the peptidic structures of p-boronophenylalanine-likeaza-amino acid (azaBPA)-containing azapeptides2019

    • Author(s)
      Miyata Kota, Narita Airi, Fujisawa Ryota, Yoshizawa Yuka, Roppongi Makoto, Ito Satoshi, Tamesue Shingo, Oba Toru
    • Organizer
      日本化学会第100回春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Synthesis and environment-sensitive fluorescence of quinolyl-phenothiazines2019

    • Author(s)
      Oba Toru, Tanazawa Kimitaka, Ito Satoshi, Tamesue Shingo
    • Organizer
      日本化学会第100回春季年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Synthesis and fluorescence properties of quinolyl-carbazoles2019

    • Author(s)
      Oba Toru, Sugawara Aki, Ito Satoshi, Tamesue Shingo
    • Organizer
      日本化学会第100回春季年会
    • Related Report
      2019 Research-status Report
  • [Remarks] 超分子化学研究室(大庭グループ)

    • URL

      http://www.chem.utsunomiya-u.ac.jp/lab/yuuki2/oba-G/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 超分子化学研究室(大庭G)

    • URL

      http://www.chem.utsunomiya-u.ac.jp/lab/yuuki2/oba-G/

    • Related Report
      2020 Research-status Report 2019 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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