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Molecular mechanism of neuroprotective activity of geldanamycin

Research Project

Project/Area Number 15K12743
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomolecular chemistry
Research InstitutionNagoya University

Principal Investigator

NISHIKAWA Toshio  名古屋大学, 生命農学研究科, 教授 (90208158)

Co-Investigator(Renkei-kenkyūsha) IMOTO Masaya  慶應義塾大学, 理工学部, 教授 (60213253)
Research Collaborator OSADA Hiroyuki  理化学研究所, 環境資源科学研究センター ケミカルバイオロジー研究グループ, グループディレクター (80160836)
MUROI Makoto  理化学研究所, 環境資源科学研究センター ケミカルバイオロジー研究グループ, 専任研究員 (30261168)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsゲルダナマイシン / 神経保護作用 / Hsp-90 / 標的同定 / ケミカルバイオロジー / HSP-90 / 2D-DIEG / プロテオーム解析
Outline of Final Research Achievements

Geldamamycin (GA), a potent inhibitor of HSP-90, shows neuroprotective effect in a low concentration. We found that an analog that removed the carbamoyl group at the 7 position also show a potent neuroprotective activity. Thus the purpose of this research is to elucidate an unknown mechanism of this neuroprotective activity by GA. We synthesized two probe molecules which contains biotin-linker on the bais of SAR of DCGA. However,pull-down assay using this biotin-probes did not give any new proteins. Proteome analysis dose not shows the difference between GA and DCGA. Thus we concluded that the neuroprotective effect by GA is induced by its binding to HSP-90 although the binding is very weak.

Report

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

    (37 results)

All 2017 2016 2015 Other

All Int'l Joint Research (3 results) Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (22 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results) Remarks (2 results)

  • [Int'l Joint Research] Chulalongkorn University/Sirinakharinwirot University(タイ)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] チュラロンコン大学/シリナカリンビロード大学(タイ)

    • Related Report
      2015 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2015 Research-status Report
  • [Journal Article] One-step Transformation of Trichloroacetamide into Isonitrile.2017

    • Author(s)
      Adachi, M.; Miyasaka, T.; Hashimoto, H.; Nishikawa, T.
    • Journal Title

      Org. Lett.

      Volume: 19 Issue: 2 Pages: 380-383

    • DOI

      10.1021/acs.orglett.6b03583

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] One-pot non-enzymatic formation of firefly luciferin in a neutral buffer from p-benzoquinone and cysteine2016

    • Author(s)
      Kanie, S., Nishikawa, T., Ojika, M., and Oba, Y.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 24794-24794

    • DOI

      10.1038/srep24794

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improved Syntheses of (+)-Iridomyrmecin and (-)-Isoiridomyrmecin, Major Components of Matatabilactone.2016

    • Author(s)
      Adachi, M.; Miyazawa, Y; Nishikawa, T.
    • Journal Title

      Nat. Prod. Commun.

      Volume: 11 Pages: 883-886

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] カスケード型環化反応による天然物合成の効率化。特集 天然物の全合成、全合成の最先端研究I2016

    • Author(s)
      西川俊夫
    • Journal Title

      化学

      Volume: 71 Pages: 40-43

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Stereocontrolled Synthesis of ABC-tricycle of Solanoeclepin A.2015

    • Author(s)
      Adachi, M.; Torii, M.; Nishikawa, T.
    • Journal Title

      Synlett

      Volume: 26 Issue: 07 Pages: 965-969

    • DOI

      10.1055/s-0034-1380399

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diastereoselective Synthesis of 3,3-Disubstituted Oxindoles from N-Aryl-3-Chlorooxindoles Bearing Axial Chirality via Nucleophilic Substitution.2015

    • Author(s)
      Nakazaki, A.; Miyagawa, K.; Nishikawa, T.
    • Journal Title

      Synlett

      Volume: 26 Issue: 08 Pages: 0-0

    • DOI

      10.1055/s-0034-1380266

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of a C-N Axially Chiral N-Aryl Isatin through Asymmetric Intramolecular N-Arylation.2015

    • Author(s)
      Nakazaki, A.; Miyagawa, K.; Miyata, N.; Nishikawa, T.
    • Journal Title

      Eur. J. Org. Chem.

      Volume: 21 Issue: 21 Pages: 4603-4606

    • DOI

      10.1002/ejoc.201500593

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 1.5-dioxaspiro[3.4]octane through bromocation-induced cascade cyclization.2015

    • Author(s)
      Nakazaki, A.; Nakane, Y.; Ishikawa, Y.; Nishikawa, T.
    • Journal Title

      Heterocycles

      Volume: 91 Issue: 6 Pages: 1157-1163

    • DOI

      10.3987/com-15-13208

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Unexpected Metal-Free Transformation of gem-Dibromomethylenes to Ketones under Acetylation Conditions.2015

    • Author(s)
      Kimura, R.; Sawayama, Y.; Nakazaki, A.; Miyamoto, K.; Uchiyama, M.; Nishikawa, T.
    • Journal Title

      Chem. Asian J.

      Volume: 10 Issue: 4 Pages: 1035-1041

    • DOI

      10.1002/asia.201403277

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multifunctionality of the N-Trichloroacetyl Group Developed in the Synthesis of Tetrodotoxin, a Puffer Fish Toxin2015

    • Author(s)
      Toshio Nishikawa, Daisuke Urabe, Masaatsu Adachi, Minoru Isobe
    • Journal Title

      Synlett

      Volume: 26 Issue: 14 Pages: 1930-1939

    • DOI

      10.1055/s-0034-1380781

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Inagami-Tamura EDLF (Endogenous Digitalis-Like Factor) の合成化学的研究: 多様な候補物質の合成2017

    • Author(s)
      橋本圭古、池田 藍、西川俊夫、中崎敦夫
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] ピロロピラジノン骨格の新規合成法とペラミンの全合成2017

    • Author(s)
      山本 雄太、中崎 敦夫、西川 俊夫
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] オシラトキシンDの合成研究2017

    • Author(s)
      新木悠介、野倉吉彦、西川俊夫
    • Organizer
      日本農芸化学会2017年度大会
    • Place of Presentation
      京都
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] トリクロロアセトアミドからイソニトリルへの新規な一段階変換反応2016

    • Author(s)
      宮坂忠親、橋本穂果、安立昌篤、西川俊夫
    • Organizer
      第47回中部化学関係学協会支部連合秋季大会
    • Place of Presentation
      豊橋
    • Year and Date
      2016-11-04
    • Related Report
      2016 Annual Research Report
  • [Presentation] Inagami-Tamura EDLF (Endogenous Digitalis-Like Factor) の合成化学的研究:ジエンを鍵中間体とした多様な候補物質の合成。2016

    • Author(s)
      橋本圭古、池田 藍、西川俊夫、中崎敦夫
    • Organizer
      日本農芸化学会中部支部第177回例会
    • Place of Presentation
      名古屋
    • Year and Date
      2016-09-24
    • Related Report
      2016 Annual Research Report
  • [Presentation] Synthetic Study on Lycojapodine A.2016

    • Author(s)
      Wen-Yu Huang, Toshio Nishikawa, Atsuo Nakazaki
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] アプリシアトキシンの合成研究2016

    • Author(s)
      野倉吉彦、西川俊夫
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] ジャガイモシスト線虫孵化促進物質ソラノエクレピンA右側部分の合成研究2016

    • Author(s)
      宮澤 悠、駒田武馬、安立昌篤、西川俊夫
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] エンドファイトが産生するアルカロイド、ペラミンの化学合成研究2016

    • Author(s)
      山本雄太、西川俊夫
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] 8-epiテトロドトキシンの合成研究2016

    • Author(s)
      岩瀬翔太郎、堀田貴大、安立昌篤、西川俊夫
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] セスペンドール芳香環部分の光学活性体の合成研究2016

    • Author(s)
      植木佳織、樋口恵子、安立昌篤、西川俊夫
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] Inagami-Tamura EDLFの合成化学的研究: 光学活性体の合成ルートの確立2016

    • Author(s)
      橋本圭古、池田 藍、西川俊夫、中崎敦夫
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] ジャガイモシスト線虫孵化促進物質ソラノエクレピンA左側部分の合成研究2016

    • Author(s)
      長谷川耕太、鳥居真衣、安立昌篤、西川俊夫
    • Organizer
      日本農芸化学会2016年度大会
    • Place of Presentation
      札幌
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] (+)-サキシトキシンの合成研究2016

    • Author(s)
      上野壮平、中崎敦夫、西川俊夫
    • Organizer
      日本化学会第96春季年会
    • Place of Presentation
      京都
    • Year and Date
      2016-03-24
    • Related Report
      2015 Research-status Report
  • [Presentation] Synthesis of biologically active steroid-derived compounds from an edible mushroom.2015

    • Author(s)
      Toshio Nishikawa, Yoshiki Nakane, Atsuo Nakazaki, Takuya Imazu, Shouta Tokoro, Ryo Sakakibara, Masaatsu Adachi, Keiichi Konoki, Mari Yotsu-Yamashita
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2015 (Pacifichem 2015)
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Synthesis and biological activities of guanidine-containing natural products.2015

    • Author(s)
      Toshio Nishikawa, Yoshiki Nakane, Atsuo Nakazaki, Takuya Imazu, Shouta Tokoro, Ryo Sakakibara, Masaatsu Adachi, Keiichi Konoki, Mari Yotsu-Yamashita
    • Organizer
      The International Chemical Congress of Pacific Basin Societies 2015 (Pacifichem 2015)
    • Place of Presentation
      Honolulu, Hawaii, USA
    • Year and Date
      2015-12-15
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Biomimetic Synthesis of Biologically Active Steroidal Natural Products.2015

    • Author(s)
      Toshio Nishikawa
    • Organizer
      ICCEOCA-10/ARNCEOCA-1
    • Place of Presentation
      Taiwan
    • Year and Date
      2015-11-02
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Syntheses of Guanidine-containing Natural Products Aiming at development of Ion-channel Blockers.2015

    • Author(s)
      Toshio Nishikawa
    • Organizer
      10th AFMC International Medicinal Chemistry Symposium (AIMECS2015)
    • Place of Presentation
      ICC JEJU, KOREA
    • Year and Date
      2015-10-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] クランベシンBカルボン酸とその誘導体の合成研究2015

    • Author(s)
      中根嘉祈、中崎敦夫、石川裕生、澤山裕介、山下まり、西川俊夫
    • Organizer
      第57回天然有機化合物討論会
    • Place of Presentation
      横浜
    • Year and Date
      2015-09-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Syntheses of Biologically Active natural products by Means of Cascade Reactions.2015

    • Author(s)
      Toshio Nishikawa
    • Organizer
      The 6th Japanese-Sino Symposium on Organic Chemistry for Young Scientists
    • Place of Presentation
      Sendai, Japan
    • Year and Date
      2015-09-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Biomimetic Synthesis of Biologically Active Steroidal Natural Products.2015

    • Author(s)
      Toshio Nishikawa
    • Organizer
      Kick-off Symposium on Advanced Research Network for Cutting-Edge Organic Chemistry in Asia
    • Place of Presentation
      Tohoku University, Japan
    • Year and Date
      2015-08-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 天然物合成と構造決定2015

    • Author(s)
      西川俊夫
    • Organizer
      静岡大学講演会
    • Place of Presentation
      静岡
    • Year and Date
      2015-04-24
    • Related Report
      2015 Research-status Report
    • Invited
  • [Remarks] 研究室HP

    • URL

      http://www.agr.nagoya-u.ac.jp/~organic/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 生物有機化学研究分野

    • URL

      http://www.agr.nagoya-u.ac.jp/~organic/

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-02-22  

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