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Scientific research on triplex-forming oligonucleotides aiming at to develop next-generation of medicines

Research Project

Project/Area Number 26460144
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Drug development chemistry
Research InstitutionNagoya University

Principal Investigator

Kodama Tetsuya  名古屋大学, 創薬科学研究科, 准教授 (00432443)

Research Collaborator MAKINO Ai  
HARA Takashi  
KONDA Tatsuya  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords人工核酸 / 構造制御 / 核酸化学 / 有機合成化学 / ヌクレオシド / 創薬化学
Outline of Final Research Achievements

We aimed to build a foundation for the next-generation of oligonucleotides drug including antigene technology by means of syntheses and evaluations of conformationally-restricted nucleosides. In this study, first, we synthesized novel nucleosides having a C4'-endo type sugar moiety or C3-endo type one. As a result of evaluating the triple-stranded oligonucleotides' stability, it was revealed that 2'-5' linked nucleic acid restricted to a C3-endo conformation, which was believed to destabilize the higher-order structure so far, can stably form a triplex did. Moreover, we clarified that the rotation angle around the glycosidic bond is a major factor determining the stability of the higher order structure by comparing the structure details of these artificial oligonucleotides with LNAs.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (9 results)

All 2017 2016 2015 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Acknowledgement Compliant: 1 results) Presentation (8 results)

  • [Journal Article] Synthesis and Properties of 7-Deazapurine- and 8-Aza-7-deazapurine-Locked Nucleic Acid Analogues: Effect of the Glycosidic Torsion Angle2017

    • Author(s)
      Takashi Hara, Tetsuya Kodama, Yumi Takegaki, Kunihiko Morihiro, Kosuke Ramon Ito, and Satoshi Obika
    • Journal Title

      The Journal of Organic Chemistry

      Volume: 82 Issue: 1 Pages: 25-36

    • DOI

      10.1021/acs.joc.6b02525

    • NAID

      120006220429

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 二面角ガンマを固定した2'-5'連結型核酸分子含有オリゴ核酸の合成とその二重鎖、三重鎖核酸の安定性2016

    • Author(s)
      牧野亜衣、廣明秀一、兒玉哲也
    • Organizer
      日本核酸医薬学会 第2回年会
    • Place of Presentation
      東京都
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] オリゴ核酸の創薬研究:化学者の立場からみる問題点とその解決に向けた 試み2016

    • Author(s)
      兒玉哲也
    • Organizer
      第 2 回名古屋大学-ラクオリア創薬シンポジウム
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2016-01-26
    • Related Report
      2015 Research-status Report
  • [Presentation] Synthetic study of 2’,5’-linked oligonucleotides containing the dihedral-angle-γ-locked ribosyl thymine2015

    • Author(s)
      牧野亜衣、廣明秀一、兒玉哲也
    • Organizer
      The 42nd International Symosium on Nucleic Acids Chemistry
    • Place of Presentation
      兵庫県姫路市
    • Year and Date
      2015-09-23
    • Related Report
      2015 Research-status Report
  • [Presentation] 6,2’‐エタノ架橋型チミジンの合成とその特性評価2015

    • Author(s)
      守屋彩子、廣明秀一、兒玉哲也
    • Organizer
      第135回日本薬学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 3',5'位間に架橋構造を導入した2'-5'結合人工核酸の合成研究2015

    • Author(s)
      牧野亜衣、廣明秀一、兒玉哲也
    • Organizer
      第135回日本薬学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 架橋型シクロヘキセニル核酸の機能性評価及び構造解析2015

    • Author(s)
      百相義大、武田修一、松本友治、廣明秀一、小比賀聡、兒玉哲也
    • Organizer
      第135回日本薬学会年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-26 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 核酸塩基の回転を制限したチミジン誘導体の合成研究2014

    • Author(s)
      兒玉哲也、守屋彩子、廣明秀一
    • Organizer
      第44回複素環化学討論会
    • Place of Presentation
      札幌
    • Year and Date
      2014-09-10 – 2014-09-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 3H2型シクロヘキセニル核酸の設計と合成、及び機能性評価2014

    • Author(s)
      百相義大、武田修一、松本友治、廣明秀一、小比賀聡、兒玉哲也
    • Organizer
      第60回日本薬学会東海支部大会
    • Place of Presentation
      鈴鹿
    • Year and Date
      2014-07-05
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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