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Studies toward creation of chemical probes for dissecting structural dynamics of ionotropic glutamate receptors

Research Project

Project/Area Number 25560418
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Chemical biology
Research InstitutionYokohama City University

Principal Investigator

OIKAWA Masato  横浜市立大学, 生命ナノシステム科学研究科, 教授 (70273571)

Co-Investigator(Kenkyū-buntansha) SAKAI Ryuichi  北海道大学, 大学院水産科学研究科, 教授 (20265721)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords化学プローブ / イオンチャネル型グルタミン酸受容体 / 人工リガンド / クリックケミストリー
Outline of Final Research Achievements

Chemical probes are important tools to elucidate functions of target proteins. Development of chemical probes for ionotropic glutamate receptor (iGluRs), that mediates majority of fast excitatory neurotransmission in the central nervous system (CNS), is highly challenging due to the unique structure of the ligand binding domain. Dysiherbaine (DH), which was isolated from Micronesian marine sponge Lendenfeldia chondrodes in 1997 by Sakai et al, is a potent agonist selective to GluK1- and GluK2-containing subtypes of kainate type iGluR. In the present study, we planned to synthesize clickable DH as a precursor for the chemical probe.
We first synthesized the vital intermediate, which has three stereocenters, performed in 10 steps starting from D-ribose. The key transformation includes domino aldol-Cannizzaro reaction followed by stereoselective aldol reaction at the ring juncture of the bicyclo[3.3.0]octane skeleton, and stereoselective addition of vinyl group to the lactol moiety.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2015 2014 2013 Other

All Journal Article (6 results) (of which Peer Reviewed: 5 results) Presentation (7 results) (of which Invited: 1 results) Remarks (2 results)

  • [Journal Article] AMPA受容体の選択的リガンド2014

    • Author(s)
      及川雅人
    • Journal Title

      ファルマシア

      Volume: 50 Pages: 1123-1127

    • NAID

      130005265995

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Damnacanthal, an effective inhibitor of LIM-kinase, inhibits cell migration and invasion.2014

    • Author(s)
      Ohashi, K.
    • Journal Title

      Mol. Biol. Cell

      Volume: 25 Issue: 6 Pages: 828-840

    • DOI

      10.1091/mbc.e13-09-0540

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Asymmetric organocatalytic cyclopropanation on chiral menthyl acrylate for the synthesis of (-)-trans-2-aminomethylcyclopropanecarboxylic acid [(-)-TAMP]2014

    • Author(s)
      Yuka Sugeno, Yuichi Ishikawa, Masato Oikawa
    • Journal Title

      Synlett

      Volume: 25 Issue: 07 Pages: 987-990

    • DOI

      10.1055/s-0033-1340953

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 1-Hydroxy-2-methyl-2-propyl Isocyanide (HMPI) as a New Convertible Isocyanide for the Ugi Four-Component-Coupling Reaction2013

    • Author(s)
      Masato Oikawa, Yutaro Sugamata, Manami Chiba, Koichi Fukushima, Yuichi Ishikawa
    • Journal Title

      Synlett

      Volume: 24 Issue: 15 Pages: 2014-2018

    • DOI

      10.1055/s-0033-1338967

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biology- and Diversity-oriented Domino Reactions for Synthesis of AMPA Receptor Antagonist IKM-159 and Analogs2013

    • Author(s)
      Masato Oikawa, Yuuki Kasori, Lisa Katayama, Etsuko Murakami, Yuya Oikawa, Yuichi Ishikawa
    • Journal Title

      Synthesis

      Volume: 45 Issue: 22 Pages: 3106-3117

    • DOI

      10.1055/s-0033-1338543

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] “First enantioselective total synthesis of (-)-dysibetaine CPa and absolute configurations of natural product2013

    • Author(s)
      6. Michihiro Sakai, Yuichi Ishikawa, Satoshi Takamizawa, Masato Oikawa
    • Journal Title

      Tetrahedron Letters

      Volume: 55 (44) Issue: 44 Pages: 5911-5912

    • DOI

      10.1016/j.tetlet.2013.08.113

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] クリッカブルダイシハーベインの合成研究2015

    • Author(s)
      ○福島孝一 及川雅人
    • Organizer
      日本化学会第95春季年会
    • Place of Presentation
      船橋
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Synthetic Study of Clickable Dysiherbaine2014

    • Author(s)
      ○福島孝一 及川雅人
    • Organizer
      3rd Chemical Biology Conference
    • Place of Presentation
      Singapore
    • Year and Date
      2014-12-15 – 2014-12-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] フルフラール類を出発原料にするシナプス受容体リガンドの開発2014

    • Author(s)
      ○及川雅人
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Clickable ダイシハーベインの合成研究2014

    • Author(s)
      ○福島孝一 石川裕一 及川雅人
    • Organizer
      日本化学会第94春季年会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
  • [Presentation] AMPA受容体阻害剤IKM-159の不斉合成2013

    • Author(s)
      ○菅俣祐太郎 石川裕一 及川雅人
    • Organizer
      第65回有機合成化学協会関東支部シンポジウム(新潟シンポジウム)
    • Place of Presentation
      新潟
    • Related Report
      2013 Research-status Report
  • [Presentation] 海綿由来GABA類縁体および部分構造の合成研究2013

    • Author(s)
      ○菅野由香 境倫宏 田中健斗 石川裕一 及川雅人
    • Organizer
      日本ケミカルバイオロジー学会第8回年会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 海綿由来GABA類縁体とその部分構造の合成研究2013

    • Author(s)
      ○菅野由香 境倫宏 田中健斗 石川裕一 及川雅人
    • Organizer
      第55回天然有機化合物討論会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Remarks] 横浜市立大学 創薬有機化学 有機化学が創薬をきりひらく

    • URL

      http://oiklab.sci.yokohama-cu.ac.jp/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 及川教授が中枢神経系シナプス受容体と選択的アンタゴニストIKM-159の分子相互作用を解明

    • URL

      http://www.yokohama-cu.ac.jp/res_pro/researcher/20130322oikawa_jmc.html

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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