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Development of small molecular ligands for simultaneous binding to the multiple sites of DNA

Research Project

Project/Area Number 16K15099
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Chemical pharmacy
Research InstitutionKyushu University

Principal Investigator

Sasaki Shigeki  九州大学, 薬学研究院, 教授 (10170672)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsリピートDNA / DNA結合分子 / 自己集積 / 協同作用 / 制限酵素 / 転写阻害 / 薬学 / 有機化学 / 核酸
Outline of Final Research Achievements

DNA repeat expansion disease is a class of human genetic disorders that arise from the vastly repeated DNA sequence such as three or five nucleotides. This study has aimed at the development of small molecular ligands that have low affinity to a single site but nonetheless, they accumulate to a multiple sites or repeated DNA site. Evaluation of cooperative binding has been investigated using the restriction enzyme AccII and DNA containing its substrate sequence. The ligands used in this study include natural product Chrmomycin A3 and the structure-simplified anthracenone derivatives. In conclusion, we have successfully demonstrated that the new synthetic ligands exhibit cooperative binding to the DNA with the multiple sequence.

Report

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

    (10 results)

All 2018 2017 2016 Other

All Journal Article (1 results) Presentation (8 results) Remarks (1 results)

  • [Journal Article] Evaluation of simultaneous binding of Chromomycin A3 to the multiple sites of DNA by the new restriction enzyme assay2018

    • Author(s)
      Hirotaka Murase, Tomoharu Noguchi, Shigeki Sasaki
    • Journal Title

      Bioorg. Med. Chem. Lett

      Volume: 28 Issue: 10 Pages: 1832-1835

    • DOI

      10.1016/j.bmcl.2018.04.013

    • Related Report
      2017 Annual Research Report
  • [Presentation] DNAリピート配列への共同的結合能を有する低分子化合物の合成と評価2018

    • Author(s)
      脇坂 元太郎 村瀬 裕貴 野口 幹晴 Ting WU 佐々木 茂貴
    • Organizer
      日本薬学会大138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 「DNA リピート配列を低分子化合物の協同効果により識別する新規戦略の構築2017

    • Author(s)
      村瀬裕貴、野口幹晴、佐々木茂貴
    • Organizer
      日本薬学会第137回年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 「リガンド間相互作用によって高リピート DNA 配列選択的に結合する低分子化合物の開発2017

    • Author(s)
      野口幹晴、村瀬裕貴、佐々木茂貴
    • Organizer
      日本薬学会第137回年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
  • [Presentation] Evaluation of cooperative binding of the smallmolecule ligands to DNA repeating sequence2017

    • Author(s)
      Hirotaka Murase  Tomoharu Noguchi  Gentaro Wakisaka Ting Wu  Shigeki Sasaki
    • Organizer
      The 1st Annual Meeting of Japan Society of Nucleic Acids Chemistry
    • Related Report
      2017 Annual Research Report
  • [Presentation] リガンド間相互作用によって高リピート配列選択的に結合する低分子化合物の開発2017

    • Author(s)
      村瀬裕貴 野口幹晴 脇坂元太郎 Ting Wu 佐々木茂貴
    • Organizer
      第34回日本薬学会九州支部大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] DNA繰り返し配列への協同的結合能を有する低分子リガンドの開発と評価2017

    • Author(s)
      脇坂元太郎 野口幹晴  村瀬裕貴  佐々木 茂貴
    • Organizer
      第54回化学関連支部合同九州大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 「二本鎖DNAリピート配列選択的に結合性を発揮する低分子リガンドの開発2016

    • Author(s)
      村瀬裕貴、野口幹晴、佐々木茂貴
    • 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
      2016-09-07
    • Related Report
      2016 Research-status Report
  • [Presentation] 低分子リガンドによるリピート配列の選択的認識2016

    • Author(s)
      村瀬裕貴、佐々木茂貴
    • Organizer
      日本ケミカルバイオロジー学会第11回年会
    • Place of Presentation
      京都
    • Year and Date
      2016-06-15
    • Related Report
      2016 Research-status Report
  • [Remarks] Bioorganic and Synthetic Chemistry

    • URL

      http://bioorg.phar.kyushu-u.ac.jp/new1.html

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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