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Catechol-O-methyltransferase Enhancer

Research Project

Project/Area Number 15K08034
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

IIJIMA Hiroshi  日本大学, 薬学部, 教授 (30465281)

Co-Investigator(Kenkyū-buntansha) 丹羽 典朗  日本大学, 薬学部, 准教授 (20541973)
齋藤 弘明  日本大学, 薬学部, 講師 (30385976)
鈴木 守  大阪大学, たんぱく質研究所, 准教授 (40280507)
小林 弘子  日本大学, 薬学部, 准教授 (50216066)
高宮 知子  日本大学, 薬学部, 講師 (50513917)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsカテコールO-メチル転移酵素 / 生成物阻害 / S-アデノシルチオニン / カテコール-O-メチル転移酵素 / COMT / 賦活化 / 腎機能障害 / 心血管系障害 / S-adenosylhomocystein / カテコール O- メチル転移酵素 / 賦活化物質 / カテコールO-メチル転位酵素 / 平衡透析
Outline of Final Research Achievements

It is known that among end-stage renal disease and preeclampsia patients the progress of the disease accompany dysfunction of catechol O-methyl transferase activity. We hypothesized that inhibition by S-adenosylhomocystein (SAH) lowers COMT activity. We searched for compounds that release the enzyme from the inhibition, the enhancers. In this study we discovered an enhancer A00607 which is more potent ever. We intend to reveal the molecular mechanism how the enhancer removes the SAH inhibition by enzyme kinetic study, equilibrium dialusis and isothermal calorimetric titration method. We proposed a theoretical model (by-pass model) and built logical model to explain mechanism of enhancement.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (7 results)

All 2018 2017 2016 2015 Other

All Presentation (5 results) Remarks (2 results)

  • [Presentation] 酵素生成物阻害 迂回路モデル2018

    • Author(s)
      飯島洋、井上雄太、齋藤栄、丹羽典朗、髙宮知子
    • Organizer
      第138回日本薬学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 化合物による「酵素反応生成物阻害」の解除2017

    • Author(s)
      見村 瑛里, 栗原 啓太, 丹羽 典朗, 高宮 知子, 飯 島 洋
    • Organizer
      第137回日本薬学会
    • Place of Presentation
      東北医科薬科大学(宮城、仙台)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Research-status Report
  • [Presentation] 化合物によるCOMT賦活化機構の検討 平衡透析による検討2016

    • Author(s)
      髙橋慶伍, 鈴木光一, 渡邉凌, 板倉利典, 歌川将之, 栗城知葉, 佐藤知幸, 高宮知子, 飯島洋
    • Organizer
      日本薬学会136年会
    • Place of Presentation
      パシフィコ横浜(神奈川 横浜)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
  • [Presentation] 化合物によるCOMT賦活化機構の検討 理論的検討2016

    • Author(s)
      鈴木光一, 髙橋慶伍,渡邉凌, 板倉利典, 歌川将之, 栗城知葉, 佐藤知幸, 高宮知子, 飯島洋
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川 横浜)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
  • [Presentation] カテコールO-メチル転移酵素賦活化物質の構造活性相関2015

    • Author(s)
      渡邉凌、鈴木光一、高橋慶伍、岩田新平、佐藤彩、姫野魁人、林誠也、板倉利典、歌川将之、栗城知葉、佐藤知幸、髙宮知子、齋藤弘明 、宮入伸一、飯島洋
    • Organizer
      日本薬学会関東支部大会
    • Place of Presentation
      日本大学薬学部(千葉 船橋)
    • Year and Date
      2015-09-12
    • Related Report
      2015 Research-status Report
  • [Remarks] 腎保護物質の探索

    • URL

      https://www.pha.nihon-u.ac.jp/research/about/activity/case-study06/

    • Related Report
      2017 Annual Research Report
  • [Remarks] 腎保護作用物質の探索

    • URL

      http://www.pha.nihon-u.ac.jp/page-973.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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