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

Research Project

Project/Area Number 16K05740
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional solid state chemistry
Research InstitutionUtsunomiya University

Principal Investigator

Toru Oba  宇都宮大学, 工学部, 教授 (30291793)

Research Collaborator NAKAI Junichi  埼玉大学, 脳抹消科学研究センター, 教授
OHKURA Masamichi  埼玉大学, 脳抹消科学研究センター, 准教授
WAKAMORI Minoru  東北大学, 歯学部, 教授
YOSHIDA Takashi  東北大学, 歯学部, 助教
MASUYA Takuto  , 大学院生
MIYATA Kota  , 大学院生
SAKAGUCHI Ryo  , 大学院生
MITOME Takahiro  , 大学院生
IWAKAMI Rino  , 大学院生
SHINOTSUKA Ryo  , 大学院生
ANJU Shintaro  , 大学院生
TANAZAWA Kimitaka  , 大学院生
NARITA Airi  , 大学院生
YOSHIZAWA Yuka  , 大学院生
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords蛍光プローブ / 膜電位 / 神経細胞 / イメージング / 超分子 / ケミカルバイオロジー / エレクトロクロミズム / 光異性化 / 光誘起電子移動 / 励起エネルギー移動 / 生態関連化学 / 超分子化学 / 膜電位感受性色素
Outline of Final Research Achievements

We synthesized novel environment-sensitive fluorophores using a unique fluorogenic core quinolyl-pyrrole (QP). The obtained dyes showed strong fluorescence solvatochromism, but their absorption spectra remained nearly unchanged. The introduction of a dimethylaminophenylethynyl moiety at the quinoline side of the QP resulted in a change in the fluorescence color from blue to red within a narrow relative permittivity range of roughly 2-10. The dye reflected voltage changes across liposomal membranes, showing a 3.7-fold enhanced fluorescence intensity when tested under the same conditions as di-4-ANEPPS, a popular voltage sensitive dye, which only changed its fluorescence intensity by a factor of 1.2. The voltage sensitivity of the dye was calculated to be 2.3%/mV. These dyes may be utilized for the studies on the activities of neurons or chloroplasts.

Academic Significance and Societal Importance of the Research Achievements

本研究により,新たな高感度膜電位感受性色素を開発する基礎ができたことは,神経回路の解析研究の進展を通して,将来の精神疾患や認知症、神経疾患の克服に資すると期待される。また,合成したキノリルピロール類の蛍光特性の解析により,これらが強いソルバトクロミズムを示すことを明らかにできた。このことは今後,高感度な膜電位感受性色素の分子設計指針の確立に利用していく予定である。さらに本研究は,蛋白質中のヒスチジン残基に選択的に反応するリンカー分子を見出した。この分子は神経細胞標的型プローブの開発だけでなく,様々な生体関連分子の開発に利用できると考えられる。

Report

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

    (37 results)

All 2019 2018 2017 2016 2015 Other

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Acknowledgement Compliant: 1 results) Presentation (24 results) Remarks (3 results)

  • [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
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of novel boron-containing mimetics of amino acids and peptides2019

    • Author(s)
      T. Oba, A. Narita, Y. Yoshizawa, K. Miyata, R. Iwakami, A. Otani, S. Tamesue, and S. Ito
    • Journal Title

      Peptide Science 2018

      Pages: 86-86

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Substrate selectivity of L-type amino acid transporters LAT1~42019

    • Author(s)
      Kota Miyata, Yuka Yoshizawa, Rino Iwakami, Promsuk Jutabha, Naohiko Anzai, and Toru Oba
    • Journal Title

      Peptide Science 2018

      Pages: 112-112

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Exploring novel compounds targeting the amino acid transporter LAT32019

    • Author(s)
      Toru Oba, Yuka Yoshizawa, Kota Miyata, Rino Iwakami, Promsuk Jutabha, and Naohiko Anzai
    • Journal Title

      Peptide Science 2018

      Pages: 111-111

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 2H-Azirines as novel His-selective orthogonal linkers and peptide mimetics2019

    • Author(s)
      Toru Oba, Shintaro Anju, Shingo Tamesue, Satoshi Ito, Hironori Tezuka, and Tomohiro Suzuki
    • Journal Title

      Peptide Science 2018

      Pages: 85-85

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Facile iodination of the vinyl groups in protoporphyrin IX dimethyl ester and subsequent transformation of the iodinated moieties2018

    • Author(s)
      Kota Miyata, Satoru Yasuda, Takuto Masuya, Satoshi Ito, Yusuke Kinoshita, Hitoshi Tamiaki, Toru Oba
    • Journal Title

      Tetrahedron

      Volume: 74 Issue: 27 Pages: 3707-3711

    • DOI

      10.1016/j.tet.2018.05.040

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Substrate recogntion of L-type amino acid transporter 3 (LAT3)2018

    • Author(s)
      Rino Iwakami, Toru Oba, Kota Miyata, Promsuk Juthaba, and Naohiko Anzai
    • Journal Title

      Peptide Science 2017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Substrate selectivity of amino acid transporter LAT32017

    • Author(s)
      Toru Oba, Rino Iwakami, Kota Miyata, Promsuk Juthaba, and Naohiko Anzai
    • Journal Title

      Peptide Science 2016

      Pages: 121-122

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Proline Drerivatives Inhibited Proliferation of Melanoma Cells2016

    • Author(s)
      Toru Oba, Kota Miyata, Rino Iwakami, Tomoko Morita, Masanori Koishikawa, and Yukihito Kabuyama
    • Journal Title

      Peptide Science 2015

      Pages: 201-202

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Development of a “Problem-Based-Learning Program without Manufacturing” in Chemistry Field2015

    • Author(s)
      大庭 亨,荷方 稔之,岩井 秀和,荒武 幸子,長谷川 和壽,原 紳,渡邊 信一,横田 和隆
    • Journal Title

      Journal of JSEE

      Volume: 63 Issue: 4 Pages: 4_27-4_32

    • DOI

      10.4307/jsee.63.4_27

    • NAID

      130005090539

    • ISSN
      1341-2167, 1881-0764
    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 膜電位計測を志向した環境応答型キノリルピロール類の開発2019

    • Author(s)
      大庭 亨,篠塚 涼, 見留隆浩,舛谷匠登,伊藤智志,為末真吾
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Synthesis and fluorescence properties of quinolylphenothiazine derivatives2019

    • Author(s)
      大庭 亨,棚沢公貴,伊藤智志,為末真吾
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Synthesis and fluorescence of novel 2-(2’-quinolyl)aryls2019

    • Author(s)
      大庭 亨,加嶋啓史,篠塚 涼,伊藤智志,為末真吾
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Synthesis of boron-containing azapeptides2019

    • Author(s)
      宮田航太,成田愛理,伊藤智志,為末真吾,大庭 亨
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Synthesis and spectroscopic properties of novel metal complexes with pi-extended ligands2019

    • Author(s)
      大庭 亨,小林稜平,伊藤智志,為末真吾
    • Organizer
      日本化学会第99春季年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Synthesis and fluorescence of boron-quinolylpyrrole complexes in comparison with boron-iminopyrrole complexes2018

    • Author(s)
      大庭 亨,棚沢公貴,篠塚 涼, 中村奈菜, 為末真吾,伊藤智志
    • Organizer
      日本化学会第98春季年会
    • Related Report
      2018 Annual Research Report 2017 Research-status Report
  • [Presentation] キノリルピロール誘導体の合成と蛍光特性,膜電位感受性色素への応用2018

    • Author(s)
      大庭 亨,篠塚 涼,見留隆浩,舛谷匠登,伊藤智志,為末真吾
    • Organizer
      第12回バイオ関連化学シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] コーチングをベースとした、世界にパラダイムシフトを起こす人材を輩出するための次世代教育の形2018

    • Author(s)
      稲垣友仁・大庭 亨
    • Organizer
      アカデミック・コーチング学会 第3回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Synthesis of novel boron-containing mimetics of amino acids and peptides”, PB-037, 10th International Peptide Symposium2018

    • Author(s)
      T. Oba, A. Narita, Y. Yoshizawa, K. Miyata, R. Iwakami, A. Otani, S. Tamesue, and S. Ito
    • Organizer
      10th International Peptide Symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] Substrate selectivity of L-type amino acid transporters LAT1~42018

    • Author(s)
      Kota Miyata, Yuka Yoshizawa, Rino Iwakami, Promsuk Jutabha, Naohiko Anzai, and Toru Oba
    • Organizer
      10th International Peptide Symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] Exploring novel compounds targeting the amino acid transporter LAT32018

    • Author(s)
      Toru Oba, Yuka Yoshizawa, Kota Miyata, Rino Iwakami, Promsuk Jutabha, and Naohiko Anzai
    • Organizer
      10th International Peptide Symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] 2H-Azirines as novel His-selective orthogonal linkers and peptide mimetics2018

    • Author(s)
      Toru Oba, Shintaro Anju, Shingo Tamesue, Satoshi Ito, Hironori Tezuka, and Tomohiro Suzuki
    • Organizer
      10th International Peptide Symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] ピリジン環の6位に官能基を有するピリジルピロール系新規蛍光色素の合成2017

    • Author(s)
      大庭 亨,畠 拓矢,伊藤 智志
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      横浜
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] アジリジン骨格を持つ神経細胞標的化合物の合成2017

    • Author(s)
      大庭 亨,安重伸太郎,鈴木智大,伊藤 智志
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      横浜
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] ボロン酸部位を持つ新規なキノリルピロールの合成とその蛍光特性2017

    • Author(s)
      大庭 亨,宮田航太,伊藤 智志
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      横浜
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] 新規な電位感受性蛍光色素の合成_フェノキサジン類およびBODIPY類の検討2017

    • Author(s)
      大庭 亨,坂口 諒,伊藤 智志
    • Organizer
      日本化学会第97春季年会
    • Place of Presentation
      横浜
    • Year and Date
      2017-03-16
    • Related Report
      2016 Research-status Report
  • [Presentation] Application of quinolyl-pyrroles as an orthogonal fluorescent sensor2017

    • Author(s)
      大庭 亨,篠塚 涼,伊藤智志
    • Organizer
      2017年光化学討論会
    • Related Report
      2017 Research-status Report
  • [Presentation] Synthesis of quinolyl-pyrroles as voltage sensitive fluorescent dyes2017

    • Author(s)
      大庭 亨,見留隆浩,舛谷匠登,伊藤智志
    • Organizer
      第11回バイオ関連化学シンポジウム
    • Related Report
      2017 Research-status Report
  • [Presentation] Substrate recogntion of L-type amino acid transporter 3 (LAT3)2017

    • Author(s)
      Rino Iwakami, Toru Oba, Kota Miyata, Promsuk Jutabha, Naohiko Anzai
    • Organizer
      the 53st Japanese Peptide Symposium
    • Related Report
      2017 Research-status Report
  • [Presentation] Substrate Selectivity of an Amino Acid Transporter LAT32016

    • Author(s)
      Toru Oba, Rino Iwakami, Kota Miyata, Promsuk Jutabha, and Naohiko Anzai
    • Organizer
      第53回ペプチド討論会
    • Place of Presentation
      京都
    • Year and Date
      2016-10-26
    • Related Report
      2016 Research-status Report
  • [Presentation] 光や放射線の応用を志向した生理活性分子の開発2016

    • Author(s)
      大庭 亨,宮田航太,見留隆弘,岩上梨乃,安重伸太郎,篠塚 涼
    • Organizer
      第1回黒潮カンファレンス
    • Place of Presentation
      千葉,九十九里町
    • Year and Date
      2016-10-22
    • Related Report
      2016 Research-status Report
  • [Presentation] Conversion of vinyl groups of protoporphyrin-IX via iodination2016

    • Author(s)
      大庭 亨,宮田航太,伊藤智志
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Place of Presentation
      金沢
    • Year and Date
      2016-09-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Synthesis of quinolyl-pyrroles as novel fluorescent melatonin analogues2016

    • Author(s)
      大庭 亨,篠塚 涼,伊藤智志
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Place of Presentation
      金沢
    • Year and Date
      2016-09-06
    • Related Report
      2016 Research-status Report
  • [Presentation] Synthesis of quinolyl-pyrroles as environmentally responsive fluorescent dyes2016

    • Author(s)
      大庭 亨,見留隆浩,舛谷匠登,伊藤智志
    • Organizer
      第10回バイオ関連化学シンポジウム
    • Place of Presentation
      金沢
    • Year and Date
      2016-09-06
    • Related Report
      2016 Research-status Report
  • [Remarks] 宇都宮大学 物質環境化学専攻 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
      2018 Annual Research 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
      2017 Research-status 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
      2016 Research-status Report

URL: 

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

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