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Development of the recognition molecules for pre-miRNA based on the hydrogen bonding

Research Project

Project/Area Number 18K14330
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 37010:Bio-related chemistry
Research InstitutionNagoya University

Principal Investigator

Murase Hirotaka  名古屋大学, 理学研究科, 特任助教 (10814486)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Keywords低分子リガンド / 分子認識 / 水素結合 / RNA 高次構造 / pre-miRNA / 蛍光プローブ / 新規RNA結合分子 / コンジュゲーション / 多機能化 / 縮合反応 / 蛍光ON型プローブ / RNA結合性低分子 / RNA高次構造
Outline of Final Research Achievements

In this study, we developed the new binding molecules that can selectively recognize the guanine base in the RNA higher-order structure. As a result, our ligands showed the high affinity to the target RNA with nM dissociation constant. Besides, our ligands showed to induce the RNA structural change and fluorescence ON response by RNA-binding. Moreover, the binding selectivity was successfully improved by ligand modifications. In this structure, a functional group was newly introduced, which can be useful for the conjugations with various other molecules.

Academic Significance and Societal Importance of the Research Achievements

RNAは様々な高次構造を形成することで、遺伝子発現に影響を与える。そのためRNAの高次構造は新たな創薬ターゲットとして注目されており、RNAに結合する新規基盤構造の開発が強く望まれている。本研究で開発した分子は、RNA結合分子の基盤構造として適用可能であり、今後様々な機能性分子とのコンジュゲーションにより多機能化が見込まれる。また、本研究で得られた知見から、本分子はRNA構造の検出プローブや、RNAの構造変化を誘起させるリガンドとしての応用も期待される。

Report

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

    (6 results)

All 2019 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Development of the binding molecules for the RNA higher-order structures based on the guanine-recognition by the G-clamp2019

    • Author(s)
      Murase Hirotaka、Nagatsugi Fumi
    • Journal Title

      Bioorganic & Medicinal Chemistry Letters

      Volume: 29 Issue: 11 Pages: 1320-1324

    • DOI

      10.1016/j.bmcl.2019.03.052

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] G-clampによるグアニン認識を基本としたRNA高次構造結合性低分子リガンドの開発2019

    • Author(s)
      村瀬 裕貴、永次 史
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 1,3-ジアザフェノキサジン環によるグアニン認識を利用したRNA高次構造検出プローブの開発2018

    • Author(s)
      村瀬 裕貴、永次 史
    • Organizer
      日本ケミカルバイオロジー学会第13回年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of fluorescent probe for RNA higher-order structure2018

    • Author(s)
      Hirotaka Murase, Fumi Nagatsugi
    • Organizer
      The 23rd International Roundtable on Nucleosides, Nucleotides and Nucleic acids
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 制限酵素阻害アッセイによるChromomycin A3の繰り返しDNAに対する同時結合性の評価2018

    • Author(s)
      村瀬 裕貴、野口 幹晴、脇坂 元太郎、Ting Wu、佐々木 茂貴
    • Organizer
      第60回天然有機化合物討論会
    • Related Report
      2018 Research-status Report
  • [Presentation] Development of small molecular G-clamp derivatives binding to RNA higher-order structure2018

    • Author(s)
      Hirotaka Murase, Fumi Nagatsugi
    • Organizer
      The 45th International Symposium on Nucleic Acids Chemistry 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2021-02-19  

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