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Development of chemicals that control the glutathione metabolism and oxidative stress and their use for chemical biology

Research Project

Project/Area Number 19310143
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Living organism molecular science
Research InstitutionKyoto University

Principal Investigator

HIRATAKE Jun  Kyoto University, 化学研究所, 教授 (80199075)

Co-Investigator(Kenkyū-buntansha) WATANABE Bunta  京都大学, 化学研究所, 助教 (10544637)
MIZUTANI Masaharu  神戸大学, 大学院・農学研究科, 准教授 (60303898)
清水 文一  京都大学, 化学研究所, 助教 (50324695)
Co-Investigator(Renkei-kenkyūsha) SHIMIZU Bunichi  東洋大学, 生命科学部, 准教授 (50324695)
Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2009: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2008: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2007: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Keywordsグルタチオン / γ-グルタミルシステイン合成酵素 / γ-グルテミルシランスペプチダーゼ / 遷移状態アナログ阻害剤 / 酸化ストレス制御 / 病原性連鎖球菌 / アンチェイジング化粧品 / 急性腎障害軽減 / γ-グルタミルトランスペプチダーゼ / 反応機構依存型阻害剤 / ヒト線維芽細胞 / 細胞レドックスポテンシャル / 急性腎障害 / 酸化ストレス / γ-グルタミルシスティン合成酵素 / 反応機構依存的阻害剤 / ホスホン酸ジエステル / 活性中心マッピング / ヒトGGT / 基質認識残基 / 部位特異的変異 / グルタミンアンタゴニスト / acivicin / X線結晶構造解析
Research Abstract

Thisstudy concerns the development and applications of chemical tools that regulate the redox status of cells by designing and synthesizing specific inhibitors of γ-glutamylcysteine synthetase (GCS), therate-determiningenzymeinglutathione synthesis, and γ-glutamyl transpeptidase (GGT), the initial andprimarily important enzyme in the glutathione metabolism.The inhibitors are to serve as chemical probes to investigate the relationships between cell redox potential and various diseases and as leads to agrochemicals and pharmaceuticals, as well as to antiaging cosmetics.

Report

(4 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • Research Products

    (29 results)

All 2010 2009 2008 2007 Other

All Journal Article (6 results) (of which Peer Reviewed: 5 results) Presentation (17 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] Crystal Structures of Escherichia coliγ-Glutamyl Transpeptidase in Complex with Azaserine and Acivicin: Novel Mechanistic Implication for Inhibition by Glutamine Antagonists.2008

    • Author(s)
      Wada K, Hiratake J, Irie M, Okada T, Yamada C, Kumagai H, Suzuki H, Fukuyama K
    • Journal Title

      J. Mol. Biol. 380

      Pages: 361-372

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystal Structures of Escherichia coli γ-Glutamyltranspeptidase in Complex with Azaserine and Acivicin : Novel Mechanistic Implication for Inhibition by Glutamine Antagonists2008

    • Author(s)
      K. Wada, et al.
    • Journal Title

      J. Mol. Biol. 380

      Pages: 361-372

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] γ-Glutamyltranspeptidase (GGT) の新規阻害剤-GGTの生理的意義をさぐる新たな化学ツール-2008

    • Author(s)
      平竹潤
    • Journal Title

      和光純薬時報 76(No. 3)

      Pages: 2-6

    • Related Report
      2008 Annual Research Report
  • [Journal Article] Crystal Structures of Escherichia coli γ-Glutamyltranspeptidase in Complex with Azaserine and Acivicin: Novel Mechanistic Implication for Inhibition by Glutamine Antagonists2008

    • Author(s)
      K. Wada, et. al.
    • Journal Title

      J. Mol. Biol. (in press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression and Biochemical Characterization of β-Primeverosidase and Application of β-Primeverosylamidine to Affinity Purification2008

    • Author(s)
      H. Saino, et. al.
    • Journal Title

      Biosci. Biotech. Biochem. 72,

      Pages: 376-383

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis and Evaluation ofγ-Phosphono Diester Analogues of Glutamate as Highly Potent Inhibitors and Active Site Probes ofγ-Glutamyl Transpeptidase.2007

    • Author(s)
      Han L, Hiratake J, Kamiyama A, Sakata K Design
    • Journal Title

      Biochemistry 46

      Pages: 1432-1447

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Presentation] 腎虚血再灌流傷害に対する新規GGT阻害剤の改善効果について2010

    • Author(s)
      山本真也, 渡辺文太, 平竹潤, 大喜多守, 松村靖夫
    • Organizer
      第83回 日本薬理学会年会 The 83rd Annual Meeting of the Japanese Pharmacological Society
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2010-03-16
    • Related Report
      2009 Annual Research Report
  • [Presentation] グルタチオン代謝の鍵酵素γ-グルタミルトランスペプチダーゼに対する古典的阻害剤アシビシンの結合様式2010

    • Author(s)
      伊田知代, 和田啓, 平竹潤, 鈴木秀之, 福山恵一
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会合同大会
    • Place of Presentation
      神戸
    • Related Report
      2009 Final Research Report
  • [Presentation] 連鎖球菌由来新規グルタチオン合成酵素とsulfoximine型遷移状態アナログ阻害剤複合体のX線結晶構造解析2009

    • Author(s)
      中島靖記, 日び隆雄, Blythe Janowiak, Owen Griffith, 平竹潤
    • Organizer
      日本農芸化学会2009年度(平成21年度)大会
    • Place of Presentation
      福岡マリンメッセ
    • Year and Date
      2009-03-28
    • Related Report
      2009 Final Research Report
  • [Presentation] 連鎖球菌由来新規グルタチオン合成酵素と sulfoximine 型遷移状態アナログ阻害剤複合体のX線結晶構造解析2009

    • Author(s)
      中島靖記, 日び隆雄, Blythe Janowiak, Owen Griffith, 平竹潤
    • Organizer
      日本農芸化学会2009年度 (平成21年度) 大会
    • Place of Presentation
      福岡マリンメッセ
    • Year and Date
      2009-03-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] 連鎖球菌由来グルタチオン合成酵素とsulfoximine型遷移状態アナログ阻害剤複合体のX線結晶構造解析2009

    • Author(s)
      中島靖記, 日び隆雄, B. Janowiak, O. Griffith, 平竹潤
    • Organizer
      日本農芸化学会2009年度 (平成21年度)大会
    • Place of Presentation
      マリンメッセ福岡
    • Year and Date
      2009-03-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] グルタチオン代謝の鍵酵素γ-グルタミルトランスペプチダーゼの阻害剤を用いた基質認識機構の解明2008

    • Author(s)
      和田啓, 入江麻智子, 中嶋麻童, 熊谷英彦, 鈴木秀之, 平竹潤, 福山恵一
    • Organizer
      BMB2008 (第31回日本分子生物学会年会・第81回日本生化学会大会合同大会)
    • Place of Presentation
      京都(京大会館)
    • Year and Date
      2008-12-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Rational Design f Specific Inhibitors ofγ-Glutamyl Transpeptidase (GGT) andγ-Glutamylcysteine Synthetase for Modulating Cellular Glutathione Redox Status.2008

    • Author(s)
      Hiratake J, Nakajima M, Han L, Kawamura N, Hibi T, Nakajima Y
    • Organizer
      2nd World Conference on Magic Bullets (Ehrlich II)
    • Place of Presentation
      Nurnberg, Germany
    • Year and Date
      2008-10-04
    • Related Report
      2009 Final Research Report
  • [Presentation] 遷移状態アナログ阻害剤を用いたγ-グルタミルトランスペプチダーゼの基質認識機構2008

    • Author(s)
      平竹潤, 中嶋麻童
    • Organizer
      第3回バイオ関連化学合同シンポジウム
    • Place of Presentation
      東京工業大学すずかけ台キャンパス
    • Year and Date
      2008-09-18
    • Related Report
      2008 Annual Research Report
  • [Presentation] γ-グルタミルシステイン合成酵素の遷移状態アナログ阻害剤-基質認識にもとづく分子設計と阻害活性-2008

    • Author(s)
      川村直裕, 平竹潤, 中島靖記, 日び隆雄, Griffith, Owen W.
    • Organizer
      日本農芸化学会2008年度(平成20年度)大会
    • Place of Presentation
      名古屋(名城大学)
    • Year and Date
      2008-03-28
    • Related Report
      2009 Final Research Report 2007 Annual Research Report
  • [Presentation] 連鎖球菌由来新規グルタチオン合成酵素のX線結晶構造解析2008

    • Author(s)
      中島靖記、可児義崇、日び隆雄、Janoviak, B.、 Griffith, O. W.、 平竹 潤
    • Organizer
      日本農芸化学会2008年度(平成20年度)大会
    • Place of Presentation
      名古屋(名城大学)
    • Year and Date
      2008-03-28
    • Related Report
      2007 Annual Research Report
  • [Presentation] γ-グルタミルトランスペプチダーゼの基質特異性と遷移状態アナログ阻害剤の分子設計2008

    • Author(s)
      平竹 潤、中嶋麻童、韓立友
    • Organizer
      日本農芸化学会関西支部 第453回 講演会
    • Place of Presentation
      京都(京大会館)
    • Year and Date
      2008-02-02
    • Related Report
      2007 Annual Research Report
  • [Presentation] Rational Design of Specific Inhibitors of γ-Glutamyl Transpeptidase (GGT) and γ-Glutamylcysteine Synthetase (GCS) for Modulating Cellular Glutathione and Redox Status2008

    • Author(s)
      Hiratake, J., Nakajima, M., Han, L., Kawamura, N., Hibi, T., Nakajima, Y.
    • Organizer
      Ehrlich II-2^<nd> World Conference on Magic Bullets
    • Place of Presentation
      Nurnberg, Germany
    • Related Report
      2008 Annual Research Report
  • [Presentation] γ-グルタミルトランスペプチダーゼ(GGT)阻害剤の分子設計と応用-GGTの生理学的役割をさぐる化学プローブになるか?-2007

    • Author(s)
      平竹 潤
    • Organizer
      京都大学化学研究所 第107回研究発表会
    • Place of Presentation
      京都大学化学研究所
    • Year and Date
      2007-12-07
    • Related Report
      2007 Annual Research Report
  • [Presentation] 酵素阻害剤をいかに分子設計し活用するか-γ-グルタミルトランスペプチダーゼの遷移状態アナログ阻害剤と活性中心マッピング-2007

    • Author(s)
      平竹 潤
    • Organizer
      静岡大学農学部セミナー
    • Place of Presentation
      静岡大学農学部
    • Year and Date
      2007-11-07
    • Related Report
      2007 Annual Research Report
  • [Presentation] 遷移状態アナログ阻害剤を用いたγ-グルタミルトランスペプチダーゼの基質認識機構2007

    • Author(s)
      中嶋麻童、韓 立友、平竹 潤
    • Organizer
      日本農芸化学会2007年度 関西・中部支部合同大会
    • Place of Presentation
      名古屋(中部大学 春日井キャンパス)
    • Year and Date
      2007-09-22
    • Related Report
      2007 Annual Research Report
  • [Presentation] Crystal structures ofγ-glutamyltranspeptidase in complexes with inhibitors and an analogue mimicking the transition state.2007

    • Author(s)
      Wada K, Hiratake J, Irie M, Okada T, Kijima K, Yamada C, Suzuki H, Kumagai H, Fukuyama K.
    • Organizer
      2nd International Symposium on Diffraction Structural Biology 2007
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-09-11
    • Related Report
      2009 Final Research Report
  • [Presentation] Crystal structures of gamma-glutamyltranspeptidase in complexes with inhibitors and an analogue mimicking the transition state2007

    • Author(s)
      Wada K, Hiratake J, Irie M, Okada T, Kijima K, Yamada C, Suzuki H, Kkumagai H, and Fukuyama K
    • Organizer
      2nd International Symposium on Diffraction Structural Biology 2007
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-09-11
    • Related Report
      2007 Annual Research Report
  • [Book] 遷移状態アナログを利用した酵素解析について, 酵素利用技術体系-基礎・解析から改変・高機能化・産業利用まで-2010

    • Author(s)
      平竹潤, 池内秀幸
    • Publisher
      エヌ・ティー・エス
    • Related Report
      2009 Final Research Report
  • [Remarks] 平竹潤「γ-Glutamyl transpeptidase(GGT)の新規阻害剤-GGTの生理的意義をさぐる新たな化学ツール」和光純薬時報76(3),2-6(2008).

    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 腎不全治療剤2010

    • Inventor(s)
      平竹潤, 渡辺文太, 松村靖夫, 大喜多守
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Industrial Property Number
      2010-032161
    • Filing Date
      2010-02-17
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 腎不全治療剤2010

    • Inventor(s)
      平竹潤, 渡辺文太, 松村靖夫
    • Industrial Property Rights Holder
      国立大学法人 京都大学
    • Industrial Property Number
      2010-032161
    • Filing Date
      2010-02-17
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 皮膚用剤組成物2009

    • Inventor(s)
      湯浅勲, 小島明子, 平竹潤
    • Industrial Property Rights Holder
      湯浅勲, 小島明子, 平竹潤
    • Industrial Property Number
      2009-105825
    • Filing Date
      2009-04-24
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] ホスホン酸ジエステル誘導体及びその製造方法2007

    • Inventor(s)
      平竹潤, 坂田完三, 韓立友
    • Industrial Property Rights Holder
      国立大学法人京都大学
    • Filing Date
      2007-06-14
    • Related Report
      2009 Final Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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