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Development of recognition molecules for 8-oxidized guanosine derivatives

Research Project

Project/Area Number 26670004
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, 薬学研究科(研究院), 教授 (10170672)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords8-オキソグアノシン / 8-オキソグアノシントリリン酸 / 8-ニトログアノシン / 8-チオグアノシン / 共有結合的捕捉 / 認識分子 / 蛍光検出 / 酸化損傷塩基 / 活性酸素 / 活性窒素 / 8-オキソグアニン / 8-ニトログアニン / 8-チオグアニン / 選択的捕捉分子
Outline of Final Research Achievements

8-Oxidized guanosine derivatives such as 8-oxo-, 8-nitro-, 8-thio- or 8-halo-2’-deoxyguanosine are markers of redox stage of cells. In this study, we have attempted to develop new recognition molecules for these 8-oxidized guanosine derivatives. In an approach, silica gels were chemically modified with 8-oxo-G clamp and were shown to selectively detect 8-oxo-dG in water.Artificial receptor molecules for 8-oxo-dG triphosphate have been successfully developed by connecting the cyclen-zinc complex with the phenoxazine skeleton.In particular, the linker structure between the cyclen-zinc complex and the phenoxazine skeleton play an important role for selectivity for 8-oxo-dG triphosphate.Development of selective molecules for covalent capture of 8-nitro-2’-deoxyguanoine was also successful using the thiol-containing molecules named 8-nitroG grasp. The chloride leaving group was introduced to the same skeleton instead of the thiol group, and shown to covalently capture 8-thio-dG.

Report

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

    (20 results)

All 2016 2015 2014 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 4 results,  Open Access: 2 results) Presentation (15 results) (of which Int'l Joint Research: 2 results) Remarks (1 results)

  • [Journal Article] New NitroG-Grasp Molecules with Enhanced Capture Reactivity for 8-Nitroguanosine in the Aqueous Media2015

    • Author(s)
      Fuchi Y. and Sasaki S.
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 63 Issue: 11 Pages: 913-919

    • DOI

      10.1248/cpb.c15-00550

    • NAID

      130005105721

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Development of New 1,3-Diazaphenoxazine Derivatives (ThioG-Grasp) to CovalentlyCapture 8-Thioguanosine2015

    • Author(s)
      Fuchi. Y, Obayashi. H and Sasaki. S
    • Journal Title

      Molecules

      Volume: 20 Issue: 1 Pages: 1078-1087

    • DOI

      10.3390/molecules20011078

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Development of New 1,3-Diazaphenoxazine Derivatives (ThioG-Grasp) to Covalently Capture 8-Thioguanosine2015

    • Author(s)
      Yasufumi Fuchi, Hideto Obayashi and Shigeki Sasaki
    • Journal Title

      Molecules

      Volume: 20 Pages: 1078-1087

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Efficient Covalent Capture of 8-Nitroguanosine via a Multiple Hydrogen-Bonded Complex2014

    • Author(s)
      Fuchi. Y and Sasaki. S
    • Journal Title

      Organic Letters

      Volume: 16 Issue: 6 Pages: 1760-1763

    • DOI

      10.1021/ol500452r

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 水中の8-oxodG特異的な検出デバイスの開発2016

    • Author(s)
      渡部卓磨、渕靖史、佐々木茂貴
    • Organizer
      日本薬学会第136回年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞中検出を目指した8-oxoGTP特異的認識分子の開発2016

    • Author(s)
      渕靖史、福田高志、佐々木茂貴
    • Organizer
      日本薬学会第136回年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Efficient covalent capture of 8-nitroguanosine via a multiple hydrogenbonded complex2015

    • Author(s)
      Yasufumi Fuchi, Shigeki Sasaki
    • Organizer
      PACIFICHEM2015
    • Place of Presentation
      ホノルル
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 8-oxodGTPを特異的に認識する蛍光性ランタノイド錯体分子の合成と評価2015

    • Author(s)
      福田高志、渕靖史、佐々木茂貴
    • Organizer
      第32回日本薬学会九州支部大会
    • Place of Presentation
      延岡
    • Year and Date
      2015-11-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] 生体内シグナル伝達に関与する8位酸化グアノシン選択的捕捉モデル分子の開発2015

    • Author(s)
      渕 靖史、大林秀都、佐々木茂貴
    • Organizer
      第32回メディシナルケミストリーシンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2015-11-26 – 2015-11-28
    • Related Report
      2014 Research-status Report
  • [Presentation] ジアザフェノキサジン環を基本骨格とする8位酸化グアノシン捕捉分子の開発2015

    • Author(s)
      渕靖史、大林秀都、佐々木茂貴
    • Organizer
      第41回反応と合成の進歩シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2015-10-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Development of1,3-diazaphenoxazine derivatives (nitroG-Grasp) for selective capture of8-nitroguanosine2015

    • Author(s)
      Yasufumi Fuchi, Shigeki Sasaki
    • Organizer
      The 42nd International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      姫路
    • Year and Date
      2015-09-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 水素結合錯体形成を介した効率的な8-チオグアノシン捕捉反応分子の開発2015

    • Author(s)
      大林秀都、渕靖史、佐々木茂貴
    • Organizer
      第52回化学関連支部合同九州大会
    • Place of Presentation
      北九州
    • Year and Date
      2015-06-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] 選択的8位酸化グアノシン捕捉モデル分子”Grasp”誘導体の開発2015

    • Author(s)
      渕靖史、大林秀都、佐々木茂貴
    • Organizer
      日本ケミカルバイオロジー学会第10回年会
    • Place of Presentation
      仙台
    • Year and Date
      2015-06-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 共有結合捕捉能をもつ8-thioguanosine認識分子の開発2015

    • Author(s)
      大林秀都、渕 靖史、佐々木茂貴
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 反応性向上を目指した新規nitroG-Grasp誘導体の合成と捕捉反応評価2015

    • Author(s)
      渕 靖史、大林秀都、佐々木茂貴
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Research-status Report
  • [Presentation] 8-thioGを特異的に捕捉する低分子プローブの開発2014

    • Author(s)
      大林秀都、渕 靖史、佐々木茂貴
    • Organizer
      第31回日本薬学会九州支部大会
    • Place of Presentation
      福岡
    • Year and Date
      2014-12-06 – 2014-12-07
    • Related Report
      2014 Research-status Report
  • [Presentation] Synthesis and evaluation of capture molecules for 8-thioguanosine2014

    • Author(s)
      Hideto Obayashi, Yasufumi Fuchi, Shigeki Sasaki
    • Organizer
      41st International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      北九州
    • Year and Date
      2014-11-05 – 2014-11-07
    • Related Report
      2014 Research-status Report
  • [Presentation] 水素結合錯体を介した効率的な8-ニトログアノシン補足反応分子の開発2014

    • Author(s)
      渕 靖史、佐々木茂貴
    • Organizer
      日本ケミカルバイオロジー学会 第9回年会
    • Place of Presentation
      大阪
    • Year and Date
      2014-06-11 – 2014-06-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 水素結合錯体形成を介した8-ニトログアノシンに対する共有結合補足分子の開発2014

    • Author(s)
      渕 靖史、佐々木茂貴
    • Organizer
      第24回万有福岡シンポジウム
    • Place of Presentation
      福岡
    • Year and Date
      2014-06-06
    • Related Report
      2014 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
      2015 Annual Research Report

URL: 

Published: 2014-04-04   Modified: 2017-05-10  

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