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Catechol-O-methyl transferase Activator; Its molecular mechanism of action.

Research Project

Project/Area Number 24590148
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) SUZUKI Mamoru  大阪大学, 蛋白質研究所, 准教授 (40280507)
TAKAMIYA Tomoko  日本大学, 薬学部, 助教 (50513917)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2012: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
KeywordsカテコールO-メチル転移酵素 / COMT / 生成物阻害 / S-アデノシルホモイステイン / カテコール-O-メチル転位酵素 / S-アデノシルメチオニン / S-アデノシルホモシステイン / 賦活化 / 腎障害 / カテコールアミン-O-メチル転位酵素 / カテコールアミン O-メチル転移酵素 / S-アデノシルホモシステイン
Outline of Final Research Achievements

Catechol-O-methyl transferase (COMT) plays a critical role in vivo to control peripheral blood concentration of noradrenaline. COMT deficiency is considered to relate with several diseases that include chronic kidney disease, atherosclerosis and cardiac insufficiency. We had discovered compounds that enhance apparent COMT reaction velocity. Enzyme kinetic study revealed that the compounds increase the dissociation of S-adenosylhomocyctein (SAH) from SAH-COMT complex. SAH is a product of COMT reaction and is at the same time a strong inhibitor that competes with S-adenosylmethione. This mechanism was confirmed by isothermal titration calorimetric experiments. Next we studied the structure-activity relationship of the enhancer compounds. During this study we found some compounds that are structurally very similar to the enhancer compounds exhibit inhibition activity. Difference of molecular volume seemed to explain the converse.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (5 results)

All 2015 Other

All Presentation (3 results) Remarks (2 results)

  • [Presentation] カテコール-O-メチル転移酵素賦活化物質2015

    • Author(s)
      板倉利典、歌川将之、栗城知葉、佐藤知幸、増田衛二、山北絵梨、髙宮知子、鈴木守、飯島洋
    • Organizer
      日本薬学会135年会
    • Place of Presentation
      神戸学院大学(兵庫 神戸)
    • Year and Date
      2015-03-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] 化合物によるカテコール-O-メチル転移酵素の賦活化

    • Author(s)
      飯島洋,増田衛二,山北絵梨,増田喬行,布施拓也,髙宮知子,寒川剛,鈴木守
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] 化合物によるカテコール-O-メチル転移酵素の賦活化

    • Author(s)
      増田喬行、布施卓也、川島洋、宮川雅樹、髙宮知子、飯島洋
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Remarks] 生体機能化学研究室HP

    • URL

      http://biofunctionalorgchem.pha.nihon-u.ac.jp/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 生体機能化学研究室HP

    • URL

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

    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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