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Development of CpG island binding molecule based on artificial dinucleotide

Research Project

Project/Area Number 26670056
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionKyushu University

Principal Investigator

Taniguchi Yosuke  九州大学, 薬学研究院, 准教授 (00452714)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords核酸医薬 / 核酸化学 / 分子認識 / 人工核酸 / 核酸誘導体 / CpGアイランド / ジヌクレオチドユニット
Outline of Final Research Achievements

In this study, we tried to create novel artificial molecules capable of binding to CpG islands deeply involved in the epigenetic regulation mechanism of gene expression. Focusing on the G/GC base triplet structure of natural type triplex DNA formation, an artificial nucleic acid analogue having an aromatic ring at the 2-position of guanosine was designed as a recognition molecule. We have succeeded in chemical synthesis of the target compound. After incorporation of them into oligonucleotide using an automated DNA synthesizer, we evaluated the interaction with duplex DNA and synthesized oligonucleotides. We found that the artificial nucleic acid containing benzene ring could recognize the GC base pair with high stability and selectivity by comparing the association constant of the natural type guanosine. Moreover, we succeeded in finding that it has recognition ability if only one is contained regardless of where it is incorporated in the oligonucleotide.

Report

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

    (9 results)

All 2016 2015 Other

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

  • [Journal Article] Aminopyridinyl-pseudodeoxycytidine derivatives selectively stabilize antiparalleltriplex DNA with multiple CG inversion sites2016

    • Author(s)
      Okamura Hidenori, Taniguchi Yosuke, Sasaki Shigeki
    • Journal Title

      Angew. Chem. Int. Ed.

      Volume: 128 Issue: 40 Pages: 12633-12637

    • DOI

      10.1002/ange.201606136

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Enhancement of TFO Triplex Formation by Conjugation with Pyrene <i>via</i> Click Chemistry2015

    • Author(s)
      Taniguchi Y, Tomizaki A, Matsueda N, Okamura H, Sasaki S
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 63 Issue: 11 Pages: 920-926

    • DOI

      10.1248/cpb.c15-00570

    • NAID

      130005105722

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] N2-フェニル置換グアノシン誘導体によるPhdG/GC3重鎖塩基対特異性の向上2016

    • Author(s)
      宮﨑芽依、谷口陽祐、佐々木茂貴
    • Organizer
      第33回日本薬学会九州支部大会
    • Place of Presentation
      鹿児島
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
  • [Presentation] Synthesis of the N2-substituted 2'-deoxyguanosine derivatives and the binding evaluation for the triplex DNA formation2016

    • Author(s)
      Mei Miyazaki, Yosuke Taniguchi, Nozomu Matsueda and Shigeki Sasaki
    • Organizer
      第43回国際核酸化学シンポジウム
    • Place of Presentation
      Kumamoto
    • Year and Date
      2016-09-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Non-natural nucleoside derivatives for selective stabilization of the antiparallel triplex DNA with multiple inversion sites2016

    • Author(s)
      Hidenori Okamura, Yosuke Taniguchi andShigeki Sasaki
    • Organizer
      The First A3 Roundtable Meeting on Chemical Probe Research Hub
    • Place of Presentation
      Fukuoka
    • Year and Date
      2016-09-22
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] GC塩基対に対する 親和性の向上を目指したN-2置換グアノシン誘導体の開発2016

    • Author(s)
      宮﨑芽依、谷口陽祐、松枝望、佐々木茂貴
    • Organizer
      第53回化学関連支部合同九州大会
    • Place of Presentation
      福岡
    • Related Report
      2016 Annual Research Report
  • [Presentation] GC塩基対に強く結合可能な人工核酸の開発2015

    • Author(s)
      宮﨑芽依、谷口陽祐、松枝望、佐々木茂貴
    • Organizer
      第32回日本薬学会九州支部大会
    • Place of Presentation
      宮﨑
    • Year and Date
      2015-11-28
    • Related Report
      2015 Research-status Report
  • [Remarks] 九州大学大学院薬学研究院生物有機合成化学分野

    • URL

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

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
  • [Remarks]

    • URL

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

    • Related Report
      2014 Research-status Report

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

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