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Design and synthesis of red fluorescent RNA-binding indicators and their application to high-throughput screening for drug discovery

Research Project

Project/Area Number 17K19133
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Inorganic/Coordination chemistry, Analytical chemistry, and related fields
Research InstitutionTohoku University

Principal Investigator

NISHIZAWA Seiichi  東北大学, 理学研究科, 教授 (40281969)

Research Collaborator SATO Yusuke  
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)
KeywordsFIDアッセイ / 深赤色蛍光インジケーター / リボソームRNA A-site / A型インフルエンザウイルスRNA / ノンコーディングRNA / 蛍光インジケーター / 検出
Outline of Final Research Achievements

We have successfully discovered that TO-PRO-3, a thiazole orange analogue with a trimethine bridge, functions as a deep-red fluorescenct indicator for the internal loop structure of the bacterial (Escherichia coli) ribosomal decoding region of the aminoacyl-tRNA site (A-site), which enables the assessment of A-site binding capability of various test compounds including blue and even-green-emitting compounds (Chem. Commun. 2019). TO-PRO-3 can also work as a useful indicator for the assessment of the binding capabilities of various test compounds for Influenza A virus RNA promoter region with a view toward the development of anti-influenza drug candidates (ChemBioChem. 2019). In addition, we have developed a new class of small heterocyclic ligands based on the 2-amino-5,6,7-trimethyl-1,8-naphthyridine structure for the bacterial A-site (Chem. Eur. J. 2018). Significantly, this ligand shows the tightest binding reported to date among non-aminoglycoside ligands.

Academic Significance and Societal Importance of the Research Achievements

本研究は、ポストゲノム時代における生命科学の飛躍的な発展を支える新しい解析技術(RNA結合リガンド)の創製を目指したものである。FID(Fluorescence indicator displacement assay)法に利用可能な深赤色蛍光インジケーター(λem > 650 nm)は世界的に報告例が無く、本研究が世界初の報告例となる。これにより、蛍光法の利点を最大限に活かしたスクリーニングが可能となるため、阻害剤開発の要となる技術基盤(スクリーニング法)を格段に発展させることが期待できる。なお、本研究成果の一部は、英国王立化学会速報誌(Chem. Commun.)の表紙にハイライトされた。

Report

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

    (14 results)

All 2019 2018 2017 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 5 results) Remarks (1 results)

  • [Journal Article] Trimethine cyanine dyes as deep-red fluorescent indicators with high selectivity to the internal loop of the bacterial A-site RNA2019

    • Author(s)
      Y. Sato, S. Yajima, A. Taguchi, K. Baba, M. Nakagomi, Y. Aiba, and S. Nishizawa
    • Journal Title

      Chemical Communications

      Volume: 55 Issue: 22 Pages: 3183-3186

    • DOI

      10.1039/c9cc00414a

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fluorescent trimethylated naphthyridine derivative with an aminoalkyl side chain as the tightest non-aminoglycoside ligand for the bacterial A-site RNA2018

    • Author(s)
      Y. Sato, M. Rokugawa, S. Ito, S. Yajima, H. Sugawara, N. Teramae, and S. Nishizawa
    • Journal Title

      Chem. Eur. J.

      Volume: 24 Issue: 52 Pages: 13862-13870

    • DOI

      10.1002/chem.201802320

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kinetic and thermodynamic analysis of triplex formation between peptide nucleic acid and double-stranded RNA2018

    • Author(s)
      Sato Takaya、Sakamoto Naonari、Nishizawa Seiichi
    • Journal Title

      Org. Biomol. Chem.

      Volume: 16 Issue: 7 Pages: 1178-1187

    • DOI

      10.1039/c7ob02912h

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] RNA解析・イメージングのための蛍光性核酸プローブの分子設計2017

    • Author(s)
      佐藤貴哉, 佐藤雄介, 西澤精一
    • Journal Title

      ぶんせき

      Volume: 2017 Pages: 459-463

    • Related Report
      2017 Research-status Report
  • [Presentation] Design and synthesis of fluorescent molecular probes for RNA binding and sensing2018

    • Author(s)
      Seiichi Nishizawa
    • Organizer
      平成30年度化学系学協会東北大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Design and Synthesis of Fluorogenic Molecular Probes for RNA sensing2018

    • Author(s)
      Seiichi Nishizawa
    • Organizer
      Seminar on Analytical Chemistry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] RNA結合リガンドの設計と合成:塩基欠損部位と三重鎖核酸形成の活用2018

    • Author(s)
      西澤精一
    • Organizer
      シンポジウム「核酸の科学」
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] RNA選択性を有する赤色蛍光モノメチンシアニン色素の開発2018

    • Author(s)
      芳野幸奈、佐藤雄介、西澤精一
    • Organizer
      日本化学会 第98春季年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 蛍光性核酸結合リガンドによるRNA検出と細胞内イメージング2017

    • Author(s)
      西澤精一
    • Organizer
      第34回 無機・分析化学コロキウム
    • Related Report
      2017 Research-status Report
  • [Presentation] TAR RNA/Tat相互作用を標的とした阻害剤スクリーニング法の開発:蛍光ラベル化ペプチドを用いた阻害能評価2017

    • Author(s)
      坂本凌平、佐藤雄介、珍田裕佳、伊藤良子、寺前紀夫、西澤精一
    • Organizer
      平成29年度日本分析化学会東北支部若手交流会
    • Related Report
      2017 Research-status Report
  • [Presentation] 蛍光性ペプチド核酸プローブによるRNA検出・イメージング2017

    • Author(s)
      西澤精一
    • Organizer
      日本分析化学会第66年会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] TAR RNA/Tat相互作用を標的とした阻害剤スクリーニング法の開発:蛍光ラベル化ペプチドを用いた阻害能評価2017

    • Author(s)
      坂本凌平、佐藤雄介、珍田裕佳、寺前紀夫、西澤精一
    • Organizer
      日本分析化学会第66年会
    • Related Report
      2017 Research-status Report
  • [Presentation] Design and synthesis of fluorescent molecular probes for RNA sensing2017

    • Author(s)
      Seiichi Nishizawa
    • Organizer
      The 17th Beijing Conference and Exhibition on Instrumental Analysis (BCEIA 2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Remarks] 細菌リボソームRNAに対して世界最強の結合力を持つ 非アミノグリコシド系小分子を開発!

    • URL

      http://www.sci.tohoku.ac.jp/news/20180927-9884.html

    • Related Report
      2018 Annual Research Report

URL: 

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

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