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Synthetic studies of the hydrophobic part of maitotoxin for elucidating its target proteins

Research Project

Project/Area Number 21350028
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Organic chemistry
Research InstitutionKyushu University (2010-2011)
Osaka University (2009)

Principal Investigator

01SHI Tohru  九州大学, 理学研究院, 教授教授 (90241520)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2011: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2009: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Keywordsマイトトキシン / ポリエーテル / 化学合成 / 分子プローブ / 作用標的分子 / 生物毒 / 膜タンパク質 / 疎水性部分 / 梯子状ポリエーテル / 膜蛋白質
Research Abstract

Maitotoxin(MTX) is a gigantic laddershaped polyether which possesses potent biological activities. Its target proteins and modeofaction at the molecular level remain unknown due to the short supply of materials from natural sources. Based on our hypothesis that whole structure of MTX is not necessary to elicit the biological activities, we developed antagonists that inhibit the biological activities induced by MTX. We designed and synthesized a partial MTX structure corresponding to the hydrophobic portion(W-C'), and an artificial laddershaped polyether(ALP) possessing heptacyclic ring systems. We have found that W-C' inhibited MTXinduced hemolytic activity, whereas the ALP inhibited MTXinduced Ca2+ influx in rat glioma C6 cells, respectively, with most potent inhibitory activities that have ever been reported.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (51 results)

All 2012 2011 2010 2009 Other

All Journal Article (26 results) (of which Peer Reviewed: 26 results) Presentation (18 results) Book (3 results) Remarks (4 results)

  • [Journal Article] Nobuaki Matsumori, Norio Tanada, Kohei Nozu, Hiroki Okazaki2011

    • Author(s)
      Design and Synthesis of Sphingomyelin-Cholesterol Conjugates and Their Formaion of Ordered Membranes
    • Journal Title

      Tohru Oishi, Michio Murata Chem. Eur. J.

      Volume: 17 Pages: 8568-8575

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conformations of Spermine in Adenosine Triphosphate Complex2011

    • Author(s)
      Tohru Oishi, and Michio Murata Chem. Eur. J.
    • Journal Title

      The Structural Basis for Weak Bimolecular Interactions of Major Cellular Electrolytes. Keisuke Maruyoshi, Toshiyuki Yamaguchi, Tetsuo Demura, Nobuaki Matsumori

      Volume: 17 Pages: 4788-4795

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Structural Reevaluation of Amphidinol 3, a Potent Antifungal Compound from Dinoflagellate. Respati2011

    • Author(s)
      T. Swasono, Mitsunori Kanemoto, Nobuaki Matsumori
    • Journal Title

      Tohru Oishi, MichioMurata Heterocycles

      Volume: 82 Pages: 1359-1369

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 6-F-ergosterol and its influence on membrane-permeabilization of amphotericin B and amphidinol 32011

    • Author(s)
      Tohru Oishi Org. Biomol. Chem
    • Journal Title

      Yusuke Kasai, Nobuaki Matsumori, Hiroyuki Ueno, Kenichi Nonomura, Shinya Yano, Murata Michio

      Volume: 9 Pages: 1437-1442

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design and Synthesis of Sphingomyelin-Cholesterol Conjugates and Their Formation of Ordered Membranes2011

    • Author(s)
      Matsumori, N., et al
    • Journal Title

      Chem Eur.J.

      Volume: 17 Issue: 31 Pages: 4788-4795

    • DOI

      10.1002/chem.201100849

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 6-F-ergosterol and its influence on membrane-permeabilization of amphotericin B and amphidinol 32011

    • Author(s)
      Kasai, Y., et al
    • Journal Title

      Org.Biomol.Chem.

      Volume: 9 Issue: 5 Pages: 1437-1442

    • DOI

      10.1039/c0ob00685h

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural reevaluations of amphidinol 3, a potent antifungal compound from dinoflagellate2011

    • Author(s)
      Swasono, R.T., et al
    • Journal Title

      Heterocycles

      Volume: 82 Issue: 2 Pages: 1359-1369

    • DOI

      10.3987/com-10-s(e)86

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Conformations of spermine in adenosine triphosphate complex : The structural basis for weak bimolecular interactions of major cellular electrolytes2011

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

      Chem.Eur.J.

      Volume: 17 Issue: 17 Pages: 4788-4795

    • DOI

      10.1002/chem.201002759

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of RaplA as a yessotoxin binding protein from blood cell membranes2010

    • Author(s)
      Yasushi Ishihama Bioorg. Med. Chem. Left
    • Journal Title

      Satoru Ujihara, Tohru Oishi, Ryota Mouri, Ric Tamate, Keiichi Konoki, Nobuaki Matsumori, Michio Murata, Yasukatsu Oshima, Naoyuki Sugiyama, Masaru Tomita

      Volume: 20 Pages: 6443-6446

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sterol Effect on Interaction between Amphidinol 3 and Liposomal Membrane as Evidenced by Surface Plasmon Resonance2010

    • Author(s)
      Respati Swasono, Ryota Mouri, Nagy Morsy, Nobuaki Matsumori
    • Journal Title

      Tohru Oishi, Michio Murata B i oo rg. Med. Chem. L ett

      Volume: 20 Pages: 2215-2218

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] SecondGeneration Synthesis of Endogenous SpermActivating and Attracting Factor2010

    • Author(s)
      Tohru Oishi, Kouichiro Ootou, Hajime Shibata, Michio Murata Tetrahedron Lett
    • Journal Title

      Isolated from the Ascidian C i on a i n testi n al i s

      Volume: 51 Pages: 2600-2602

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reductive Etherification under Microfluidic Conditions2010

    • Author(s)
      Tomovoshi Imaizumi, Michio Murata C h em. L ett
    • Journal Title

      Application to Practical Synthesis of the FGHIJ-Ring System of Yessotoxin

      Volume: 39 Pages: 108-109

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reductive Etherification under Microfluidic Conditions : Application to Practical Synthesis of the FGHIJ-Ring System of Yessotoxin.2010

    • Author(s)
      Tohru Oishi, et al.
    • Journal Title

      Chem.Lett.

      Volume: 39 Pages: 108-109

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Second-Generation Synthesis of Endogenous Sperm-Activating and Attracting Factor (SAAF) Isolated from the Ascidian Ciona intestinalis.2010

    • Author(s)
      Tohru Oishi, et al.
    • Journal Title

      Tetrahedron Lett.

      Volume: 51 Pages: 2600-2602

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sterol Effect on Interaction between Amphidinol 3 and Liposomal Membrane as Evidenced by Surface Plasmon Resonance.2010

    • Author(s)
      Respati Swasono, et al.
    • Journal Title

      Bioorg.Med.Chem.Lett.

      Volume: 20 Pages: 2215-2218

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stereoselective Synthesis of the C31C40/C43-052 Unit of Amphidinol 32009

    • Author(s)
      Tohru Oishi J. Org. Chem
    • Journal Title

      Mitsunori Kanemoto, Michio Murata

      Volume: 74 Pages: 8810-8813

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Direct Interaction between Amphotericin B and Ergosterol in Lipid Bilayers As Revealed by 2H NMR Spectroscopy. Nobuaki Matsumori, Kazuaki Tahara2009

    • Author(s)
      Tohru Oishi, Michio Murata J. Am. Chem. Soc
    • Journal Title

      Hiroko Yamamoto, Atsushi Morooka, Mototsugu Doi

      Volume: 131 Pages: 1185511860-1185511860

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ion Channel Complex of Antibiotics as Viewed by NMR2009

    • Author(s)
      Tohru Oishi Pure Appl. Chem
    • Journal Title

      Michio Murata, Yusuke Kasai, Yuichi Umegawa, Naohiro Matsushita, Hiroshi Tsuchikawa, Nobuaki Matsumori

      Volume: 81 Pages: 1123-1129

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Surface Plasmon Resonance-Based Detection of LadderShaped Polyethers by Inhibition Detection Method. Ryota Mouri2009

    • Author(s)
      Tohru Oishi, Kohei Torikai, Satoru Ujihara, Nobuaki Matsumori, Michio Murata
    • Journal Title

      Yasukatsu Oshima B ioorg. Med. Chem. L ett

      Volume: 19 Pages: 2824-2828

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] MaitotoxinPhotoactive Probe Binds to Membrane Proteins in Blood Cells. Keiichi Konoki, Masaki Hashimoto2009

    • Author(s)
      Tohru Oishi, Michio Murata H eter oc yc l es
    • Journal Title

      Kaori Honda, Kazuo Tachibana, Rie Tamate, Futoshi Hasegawa

      Volume: 79 Pages: 1007-1017

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conformational Change of Spermidine upon Interaction with Adenosine Triphosphate in Aqueous Solution. Keisuke Maruyoshi2009

    • Author(s)
      Tohru Oishi, Michio Murata Chem. E ur. J.
    • Journal Title

      Kaori Nonaka, Takeshi Sagane, Tetsuo Demura, Toshiyuki Yamaguchi, Nobuaki Matsumori

      Volume: 15 Pages: 1618-1626

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design, Synthesis, and Biological Evaluation of Fluorinated Analogues of Salicylihalamide2009

    • Author(s)
      Tohru Oishi J. Med. Chem.
    • Journal Title

      Yoshinori Sugimoto, Keiichi Konoki, Michio Murata, Masafumi Matsushita, Hiroshi Kanazawa

      Volume: 52 Pages: 798-806

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of 25-13CAmphotericin B Methyl Ester2009

    • Author(s)
      Tohru Oishi Chem. L ett
    • Journal Title

      A Molecular Probe for Solid-state NMR Measurements. Naohiro Matsushita, Yukiko Matsuo, Hiroshi Tsuchikawa, Nobuaki Matsumori, Michio Murata

      Volume: 38 Pages: 114-115

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Maitotoxin-photoactive probe binds to membrane proteins in blood cells.2009

    • Author(s)
      Keiichi Konoki, et al.
    • Journal Title

      Heterocycles 79

      Pages: 1007-1017

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Surface plasmon resonance-based detection of ladder-shaped polyethers by inhibition detection method.2009

    • Author(s)
      Ryota Mouri, et al.
    • Journal Title

      Bioorg.Med.Chem.Lett. 19

      Pages: 2824-2828

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stereoselective Synthesis of the C31-C40/C43-C52 Unit of Amphidinol 3.2009

    • Author(s)
      Mitsunori Kanemoto, et al.
    • Journal Title

      J.Org.Chem. 74

      Pages: 8810-8813

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Synthesis and Biology of Laddershaped Polyethers Isolated from Marine Dinoflagellate for Exploring Biological Functions2012

    • Author(s)
      Tohru Oishi, Mona Symposium
    • Organizer
      Natural Products and Medicinal Chemistry
    • Place of Presentation
      University of West Indies, Mona, Kinuston, Jamaica
    • Year and Date
      2012-03-06
    • Related Report
      2011 Final Research Report
  • [Presentation] Synthesis and Biology of Ladder-shaped Polyethers Isolated from Marine Dinoflagellate for Exploring Biological Functions2012

    • Author(s)
      Oishi, T.
    • Organizer
      Mona Symposium : Natural Products and Medicinal Chemistry
    • Place of Presentation
      Kingstone, Jamaica(招待講演)
    • Year and Date
      2012-01-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新学術領域反応集積化の合成化学革新的手法の開発と有機物質創成への展開平成22年度第2回成果報告会(招待講演)2011

    • Author(s)
      大石徹
    • Organizer
      梯子状ポリエーテル天然物のマイクロフロー合成
    • Place of Presentation
      早稲田大学
    • Year and Date
      2011-11-30
    • Related Report
      2011 Final Research Report
  • [Presentation] 膜タンパク質との相互作用解明を志向した梯子状ポリエーテルの合成研究2011

    • Author(s)
      大石徹
    • Organizer
      有機合成夏季セミナー「明日の有機合成化学」(招待講演)
    • Place of Presentation
      大阪科学技術センター,大阪
    • Year and Date
      2011-09-06
    • Related Report
      2011 Final Research Report
  • [Presentation] 膜タンパク質との相互作用解明を志向した梯子状ポリエーテルの合成研究2011

    • Author(s)
      大石徹
    • Organizer
      有機合成夏季セミナー「明日の有機合成化学」
    • Place of Presentation
      大阪科学技術センター,大阪(招待講演)
    • Year and Date
      2011-09-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] 細胞膜に作用する生理活性天然物の合成化学的アプローチによる構造決定2011

    • Author(s)
      大石徹
    • Organizer
      高知大学「IMT & 統合的バイオイメージング合同シンポジウム」(招待講演)
    • Place of Presentation
      高知大学,朝倉キャンパス,高知
    • Year and Date
      2011-07-02
    • Related Report
      2011 Final Research Report
  • [Presentation] 細胞膜に作用する生理活性天然物の合成化学的アプローチによる構造決定2011

    • Author(s)
      大石徹
    • Organizer
      高知大学「IMT&統合的バイオイメージング合同シンポジウム」
    • Place of Presentation
      高知大学,高知(招待講演)
    • Year and Date
      2011-07-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] Synthetic Approach toward Structure Confirmation of Amphidinol 32011

    • Author(s)
      Oishi, T.
    • Organizer
      The Sixth Korea-Japan Young Scientists Meeting on Natural Products Chemistry and Bioorganic Chemistry
    • Place of Presentation
      Seoul, Korea(一般講演)
    • Year and Date
      2011-06-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] An Aproach Based on Organic Synthesis toward Identification of Target Proteins of Maitotoxin2011

    • Author(s)
      Oishi, T.
    • Organizer
      The Uehara Memorial Foundation Symposium 2011
    • Place of Presentation
      Tokyo, Japan(招待講演)
    • Year and Date
      2011-06-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新学術領域反応集積化の合成化学革新的手法の開発と有機物質創成への展開第3回若手シンポジウム(九州地区)(招待講演)2011

    • Author(s)
      大石徹
    • Organizer
      梯子状ポリエーテルのフローマイクロ合成
    • Place of Presentation
      九州大学先導物質化学研究所
    • Year and Date
      2011-02-05
    • Related Report
      2011 Final Research Report
  • [Presentation] An Aproach Based on Organic Synthesis toward Identification of Target Proteins of Maitotoxin2011

    • Author(s)
      Tohru Oishi
    • Organizer
      The Uehara Memorial Foundation Symposium 2011 Chembiomolecular Science : at the Frontier of Chemistry and Biology
    • Place of Presentation
      Hyatt Regency Tokyo, Tokyo, Japan
    • Related Report
      2011 Final Research Report
  • [Presentation] The Sixth Korea-Japan Young Scientists Meeting on Natural Products Chemistry and Bioorganic Chemistry(一般講演)2011

    • Author(s)
      Tohru Oishi
    • Organizer
      Synthetic Approach toward Structure Confirmation of Amphidinol 3
    • Place of Presentation
      Seoul National University, Seoul, Korea
    • Related Report
      2011 Final Research Report
  • [Presentation] Pacifichem 2010(tBT A IAA)2010

    • Author(s)
      Tohru Oishi
    • Organizer
      Synthesis and Biology of Laddershaped Polyethers Isolated from Marine Dinoflagellate for Exploring Biological Functions
    • Place of Presentation
      Hawaii, USA
    • Year and Date
      2010-12-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Synthesis and Biology of Ladder-shaped Polyethers Isolated from Marine Dinoflagellate for Exploring Biological Functions2010

    • Author(s)
      Tohru Oishi
    • Organizer
      Pacifichem 2010
    • Place of Presentation
      Hawaii, USA
    • Year and Date
      2010-12-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] マイクロフローリアクターを用いた梯子状ポリエーテル天然物合成の効率化2010

    • Author(s)
      大石徹
    • Organizer
      フローマイクロ合成研究会第46回研究会(招待講演)
    • Place of Presentation
      大阪科学技術センター,大阪
    • Year and Date
      2010-06-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Synthesis and Biology of Ladder-shaped Polyethers Isolated from Dinoflagellates2010

    • Author(s)
      Tohru Oishi
    • Organizer
      Gordon Research Conference Marine Natural Products(VI T p)
    • Place of Presentation
      Ventura Beach Marriott, Ventura, CA, USA
    • Year and Date
      2010-02-28
    • Related Report
      2011 Final Research Report
  • [Presentation] Synthesis and Biology of Ladder-shaped Polyethers Isolated from Dinoflagellates2009

    • Author(s)
      Tohru Oishi
    • Organizer
      Gordon Research Conference Marine Natural Products(VI T p)
    • Place of Presentation
      Kyoto Japan, November
    • Year and Date
      2009-11-11
    • Related Report
      2011 Final Research Report
  • [Presentation] Synthetic Studies of Yessotoxin and Maitotoxin2009

    • Author(s)
      Tohru Oishi
    • Organizer
      The 11th International KYOTO Conference of New Aspects of Organic Chemistry (IKCOC-11)
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2009-11-11
    • Related Report
      2009 Annual Research Report
  • [Book] ソレル有機化学 第五章化学反応と機構2009

    • Author(s)
      Thomas N. Sorrell
    • Publisher
      東京化学同人
    • Related Report
      2011 Final Research Report
  • [Book] 膜タンパク質との相互作用解明を志向した梯子状ポリエーテルの設計・合成・活性評価2009

    • Author(s)
      大石徹・鳥飼浩平・長谷川太志
    • Publisher
      有機合成化学協会
    • Related Report
      2011 Final Research Report
  • [Book] ソレル 有機化学 上 (第5章 化学反応と機構)2009

    • Author(s)
      ソレル著(木越・佐々木・村田・石橋監訳)
    • Total Pages
      34
    • Publisher
      東京化学同人
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://ww.scc.kyushu-u.ac.jp/seibutsuyuki/idex.htm

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.scc.kyushu-u.ac.jp/Seibutsuyuki/index.htm

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.scc.kyushu-u.ac.jp/Seibutsuyuki/index.htm

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.ch.wani.osaka-u.ac.jp/lab/murata/

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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