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A study on the biosynthesis of guanosine monophosphate and the development of functional molecules targeting guanosine monophosphate synthetase

Research Project

Project/Area Number 17K05929
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Bio-related chemistry
Research InstitutionGifu University

Principal Investigator

Oka Natsuhisa  岐阜大学, 工学部, 准教授 (50401229)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords核酸の生合成 / カルボニル基のリン酸化 / ヌクレオチド / 酵素応答性分子 / キサントシン / 7-デアザグアニン / グアノシン一リン酸 / キサントシン一リン酸 / GMP合成酵素 / AMP-XMP / グアノシン一リン酸合成酵素 / リン酸化 / 抗がん剤
Outline of Final Research Achievements

Appropriately protected xanthosine derivatives were reacted with phosphoramidites activated by N-(cyanomethyl)dimethylammonium triflate (CMMT) developed by us. Subsequent oxidation/sulfurization and deprotection of the resultant phosphate esters afforded 2-O-phosphoryl/thiophosphorylxanthosine derivatives. The products were also fully deprotected by TBAF to afford xanthosine 2-phosphates. This new phosphorylation reaction should be useful for the development of molecular probes and therapeutic agents targeting the biosynthesis of guanosine monophosphate. Furthermore, a regioselective protection of 7-deazaguanine derivatives was achieved by using diphenylcarbamoyl chloride and DMAP. The appropriately protected 7-deazaguanine derivatives thus obtained were applied to the synthesis of 7-deazaguanosine derivatives which should be useful for the synthesis of 7-deazaxanthosine derivatives.

Academic Significance and Societal Importance of the Research Achievements

本研究で開発した手法は、キサントシンの2位カルボニル基の初のリン酸化反応であり、グアノシン一リン酸の生合成中間体であるAMP-XMPの化学合成に欠かせない。また、本反応はAMP-XMPそのものだけでなく、その化学修飾アナログの合成にも応用できる。この様な化学修飾アナログは、グアノシン一リン酸の生合成経路を標的とする分子プローブや分子標的薬の合成への応用が期待される。以上のことから、本研究の成果は、これまで直接的な研究が難しかったグアノシン一リン酸の生合成中間体の性質や機能により詳細に迫るきっかけとなると同時に、この生合成経路を標的とする医薬品開発への道を拓くものであり、極めて意義深いと言える。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2020 2019 2018 2017 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (12 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Regioselective O6-diphenylcarbamoylation of 7-deazaguanine derivatives via a stable intermediate 1-(diphenylcarbamoyl)-4-(dimethylamino)pyridinium chloride2020

    • Author(s)
      Oka Natsuhisa、Nakano Koki、Fukuta Akane、Ando Kaori
    • Journal Title

      Tetrahedron Letters

      Volume: N/A Issue: 28 Pages: 152085-152085

    • DOI

      10.1016/j.tetlet.2020.152085

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a radical SAM enzyme involved in the synthesis of archaeosine2019

    • Author(s)
      Yokogawa Takashi、Nomura Yuichiro、Yasuda Akihiro、Ogino Hiromi、Hiura Keita、Nakada Saori、Oka Natsuhisa、Ando Kaori、Kawamura Takuya、Hirata Akira、Hori Hiroyuki、Ohno Satoshi
    • Journal Title

      Nature Chemical Biology

      Volume: 15 Issue: 12 Pages: 1148-1155

    • DOI

      10.1038/s41589-019-0390-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] キサントシンの2位カルボニル基のリン酸化反応の開発2019

    • Author(s)
      平林 洋紀・岡 夏央・安藤 香織
    • Organizer
      2019年度有機合成化学北陸セミナー
    • Related Report
      2019 Annual Research Report
  • [Presentation] Stereoselective furanosylation reactions for the synthesis of oligosaccharides and nucleosides2019

    • Author(s)
      Natsuhisa Oka
    • Organizer
      The 8th International Conference of The Indonesian Chemical Society (ICICS) 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Synthesis of 7-deazaguanosine derivatives via glycosylation2019

    • Author(s)
      Koki Nakano, Natsuhisa Oka, Akane Fukuta, Ayumi Mori, Kaori Ando
    • Organizer
      The 4th International Symposium on Process Chemistry (ISPC2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 7-デアザグアノシン誘導体の合成法の開発2018

    • Author(s)
      中野 宏紀・岡 夏央・福田 茜・安藤 香織
    • Organizer
      第49回中部化学関係学協会支部連合秋季大会
    • Related Report
      2018 Research-status Report
  • [Presentation] キサントシンの2位カルボニル基のリン酸化反応の開発2018

    • Author(s)
      平林 洋紀・岡 夏央・安藤 香織
    • Organizer
      第49回中部化学関係学協会支部連合秋季大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Synthesis of 7-deazaguanosine derivatives2018

    • Author(s)
      Natsuhisa Oka, Kouki Nakano, Akane Fukuta, Ayumi Mori, Kaori Ando
    • Organizer
      The 45th International Symposium on Nucleic Acid Chemistry (ISNAC2018)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Stereocontrolled Synthesis of P-Chiral Oligonucleotides2017

    • Author(s)
      Natsuhisa Oka
    • Organizer
      International Symposium on Pure & Applied Chemistry 2017 (ISPAC 2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Stereoselective synthesis of α-ribofuranosides2017

    • Author(s)
      岡 夏央
    • Organizer
      2017分子化学研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] ストレプトマイセス属細菌由来α-リボフラノシドの合成研究2017

    • Author(s)
      神藤 優花・岡 夏央・安藤 香織
    • Organizer
      第48回中部化学関係学協会支部連合秋季大会
    • Related Report
      2017 Research-status Report
  • [Presentation] キラル酸活性化剤を用いるジヌクレオシドホスホロチオエートの立体選択的合成2017

    • Author(s)
      鈴木 康佑・岡 夏央・安藤 香織
    • Organizer
      第48回中部化学関係学協会支部連合秋季大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 不斉ヨードラクトン化を経由するホモクエン酸ラクトンの合成研究2017

    • Author(s)
      見須 亮太・岡 夏央・孕石 英義・安藤 香織
    • Organizer
      第48回中部化学関係学協会支部連合秋季大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Synthesis of 7-deazaguanine and 7-deazaguanosine derivatives2017

    • Author(s)
      Natsuhisa Oka, Akane Fukuta, Kaori Ando
    • Organizer
      The 44th International Symposium on Nucleic Acid Chemistry (ISNAC2017)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 岐阜大学 工学部 化学・生命工学科 安藤研究室 ホームページ

    • URL

      https://www1.gifu-u.ac.jp/~ando_ap/

    • Related Report
      2019 Annual Research Report 2017 Research-status Report
  • [Remarks] 岐阜大学工学部化学・生命工学科安藤研究室ホームページ

    • URL

      https://www1.gifu-u.ac.jp/~ando_ap/

    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] シクロペンテン誘導体及びシクロペンテン誘導体の製造方法2019

    • Inventor(s)
      岡 夏央、安藤 香織
    • Industrial Property Rights Holder
      岡 夏央、安藤 香織
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-199474
    • Filing Date
      2019
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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