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Development of biomimetic cocktail reagent to screen potential risks of drugs

Research Project

Project/Area Number 25670008
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Physical pharmacy
Research InstitutionTohoku University

Principal Investigator

OE Tomoyuki  東北大学, 薬学研究科(研究院), 教授 (10203712)

Co-Investigator(Kenkyū-buntansha) GOTO Takaaki  東北大学, 大学院薬学研究科, 講師 (40344684)
LEE Seon Hwa  東北大学, 大学院薬学研究科, 助教 (60519776)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords反応性代謝物 / トラッピング試薬 / カクテル試薬 / 質量分析
Outline of Final Research Achievements

Background・Aim: Reactive metabolites of drugs result in adverse drug reactions through the formation of covalent biding to biological macromolecules. Therefore, trapping assays, such as glutathione trapping method, are widely performed together with LC-MS for the screening. However, the current strategy still has problems: ex. low throughput, structural gap between trapping reagents and biological macromolecules, and metabolic degradation of the reagents. We therefore aimed to develop a high-throughput/hybrid screening system to solve the problems. Outcome: I) Using simple motif of each nucleophilic site followed by mixing as a cocktail, the structural gap and metabolic degradation were avoided. II) Concomitant use of the stable isotope labeled motifs facilitated the screening because of the characteristic doublet peaks. III) Isotope pattern dependent scanning enabled the automated MS/MS analysis using the characteristic doublet peaks.

Report

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

    (13 results)

All 2015 2014 2013 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (8 results) (of which Invited: 7 results) Remarks (4 results)

  • [Journal Article] Predicted multiple selected reaction monitoring to screen activated drug-mediated modifications on human serum albumin.2014

    • Author(s)
      Fumio Osaki, Takaaki Goto, Seon Hwa Lee and Tomoyuki Oe
    • Journal Title

      Analytical Biochemistry

      Volume: 449 Pages: 59-67

    • DOI

      10.1016/j.ab.2013.12.016

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 生体高分子の化学修飾解析:バイオマーカー研究と毒性学研究の接点2015

    • Author(s)
      大江知行
    • Organizer
      第42回日本毒性学会学術年会
    • Place of Presentation
      石川県金沢市
    • Year and Date
      2015-06-29 – 2015-07-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] アミノ酸の修飾解析を通したバイオマーカー研究2014

    • Author(s)
      大江知行
    • Organizer
      「新アミノ酸分析研究会」第4回学術講演会
    • Place of Presentation
      東京都文京区
    • Year and Date
      2014-11-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 分子カルテ:タンパク質を生体内イベントの記録媒体と考える化学修飾解析2014

    • Author(s)
      大江知行
    • Organizer
      日本食品科学工学会 第61回大会
    • Place of Presentation
      福岡県福岡市
    • Year and Date
      2014-08-28 – 2014-08-30
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] タンパク質を精密分析してわかる事2014

    • Author(s)
      大江知行
    • Organizer
      第31 回無機・分析化学コロキウム
    • Place of Presentation
      宮城県大崎市
    • Year and Date
      2014-05-30 – 2014-05-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] タンパク質を精密分析してわかる事2014

    • Author(s)
      大江知行
    • Organizer
      第31 回無機・分析化学コロキウム
    • Place of Presentation
      東北大学川渡共同セミナーセンター(宮城県大崎市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 分子カルテ:タンパク質を生体内イベントの記録媒体と考える化学修飾解析2014

    • Author(s)
      大江知行
    • Organizer
      日本食品科学工学会第61回大会
    • Place of Presentation
      中村学園大学(福岡県福岡市城南区)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 質量分析だから出来る薬物動態研究とバイオマーカー探索~演者の研究例から~2013

    • Author(s)
      大江知行
    • Organizer
      第61回質量分析総合討論会
    • Place of Presentation
      つくば国際会議場(茨城県つくば市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 質量分析によるタンパク質・ペプチドの精密定量分析

    • Author(s)
      大江知行
    • Organizer
      第45回日本臨床検査医学会東北支部総会および第24回日本臨床化学会東北支部総会
    • Place of Presentation
      KKRホテル仙台(宮城県仙台市青葉区)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] 東北大学研究者紹介>著書論文等

    • URL

      http://db.tohoku.ac.jp/whois/view?l=ja&u=4c4f82fe08ba4b967929dec143f0c259&c=0

    • Related Report
      2014 Annual Research Report
  • [Remarks] 東北大学大学院薬学研究科・薬学部HP>臨床分析化学分野>学術活動

    • URL

      http://www.pharm.tohoku.ac.jp/~bunseki/gakujutukatudou.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] (1) 東北大学大学院薬学研究科臨床分析化学分野ホームページ

    • Related Report
      2013 Research-status Report
  • [Remarks] (2) 東北大学研究者紹介

    • Related Report
      2013 Research-status Report

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

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