Development of selective phosphatase inhibitor based on calyculin A

• Project/Area Number: 23710250
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Living organism molecular science
• Research Institution: The University of Tokyo
• Principal Investigator: TOSHIYUKI Wakimoto 東京大学, 大学院・薬学系研究科, 准教授 (70363900)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: カリクリン / タンパク質脱リン酸化酵素 / チョコガタイシカイメン / Calyculin A / 蛍光プローブ / 海綿

Research Abstract

Many marine natural products exhibit highly potent cytotoxicity. They selectively inhibit the functions of either intracellular or membrane-bound target molecules, leading to cell death. These specific biological activities can provide valuable information on the biochemical research field. Therefore, we initiated this program aimed at the development of functionalized calyculin A, a protein phosphatase inhibitor, which was originally isolated from the marine sponge, Discodermia calyx. Based on the insights into the structural moieties essential for biological activity, the synthetic process toward library construction and fluorescent probe were developed.

Research Products

• [Journal Article] Allos-hemicalyculin A, a photochemically converted calyculin from the marine sponge Discodermia calyx (2013)
  • Author(s): M. Kimura, T. Wakimoto, I. Abe
  • Journal Title: Tetrahedron Lett. Volume: 54 Issue: 1 Pages: 114-116
  • DOI: 10.1016/j.tetlet.2012.10.130
  • Peer Reviewed
• [Journal Article] Heterologously expressed β-hydroxyl fatty acids from a metagenomic library of a marine sponge (2012)
  • Author(s): R. He, T. Wakimoto, Y. Egami, H. Kenmoku, T. Ito, Y. Asakawa, I. Abe
  • Journal Title: Bioorg. Med. Chem. Lett. Volume: 22 Issue: 24 Pages: 7322-7325
  • DOI: 10.1016/j.bmcl.2012.10.082
  • Peer Reviewed
• [Journal Article] Porphyrins from a metagenomic library of the marine sponge Discodermia calyx (2012)
  • Author(s): He, R.
  • Journal Title: Mol. BioSyst. Volume: 6 Issue: 9 Pages: 2334-2338
  • DOI: 10.1039/c2mb25169h
  • Peer Reviewed
• [Journal Article] Calyxamides A and B, cytotoxic cyclic peptides from the marine sponge Discodermia calyx (2012)
  • Author(s): M. Kimura, T. Wakimoto, Y. Egami, K. C. Tan, Y. Ise, I. Abe
  • Journal Title: J. Nat. Prod. Volume: 75 Issue: 2 Pages: 290-294
  • DOI: 10.1021/np2009187
  • Peer Reviewed
• [Journal Article] Labile natural products. (2012)
  • Author(s): T. Wakimoto, I. Abe
  • Journal Title: MedChemComm Volume: 3 Issue: 8 Pages: 866-870
  • DOI: 10.1039/c2md20016c
  • Peer Reviewed
• [Journal Article] Engineering of plant type III polyketide synthases. (2012)
  • Author(s): T. Wakimoto, H. Morita, I. Abe
  • Journal Title: Methods in Enzymology Volume: 515 Pages: 337-358
  • Peer Reviewed
• [Journal Article] Furan fatty acid as an anti-inflammatory component from green-lipped mussel Perna canaliculus (2011)
  • Author(s): Wakimoto, T., Kondo, H., Nii, H., Kimura, K., Egami, Y., Oka, Y., Yoshida, M., Kida, E., Ye, Y.-p., Akahoshi, S., Asakawa, T., Matsumura, K., Ishida, H., Nukaya, H., Tsuji, K., Kan, T., Abe, I.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 108 Issue: 42 Pages: 17533-17537
  • DOI: 10.1073/pnas.1110577108
  • Peer Reviewed
• [Journal Article] Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase (2011)
  • Author(s): Morita, H., Yamashita, M., Shi, S.-P., Wakimoto, T., Kondo, S., Kato, R., Sugio, S., Kohno, T., Abe, I.
  • Journal Title: Proc.Natl.Acad.Sci.USA Volume: 108 Issue: 33 Pages: 13504-13509
  • DOI: 10.1073/pnas.1107782108
  • Peer Reviewed
• [Journal Article] Enantioselective Total Synthesis of Aperidine (2011)
  • Author(s): Toshiyuki Wakimoto, Kakeru Miyata, Hitoshi Ouchi, Tomohiro Asakawa, Haruo Nukaya, Yoshihide Suwa and Toshiyuki Kan
  • Journal Title: Organic Letters Volume: 13 Issue: 10 Pages: 2789-2791
  • DOI: 10.1021/ol200728w
  • Peer Reviewed
• [Presentation] Calyculin A 生合成遺伝子ク ラスターの探索 (2012)
  • Author(s): 脇本敏幸
  • Organizer: 日本薬学会第 132 年会
  • Place of Presentation: (札幌)シンポジウム
  • Year and Date: 2012-03-30
• [Presentation] Calyculin Aの構造を基にした化合物ライブラリー構築による選択的ホスファターゼ阻害剤の創製 (2012)
  • Author(s): 村松孝洋、脇本敏幸、阿部郁朗
  • Organizer: 日本生薬学会 第59年会
  • Place of Presentation: 千葉
• [Presentation] 不安定天然物の探索 (2012)
  • Author(s): 脇本敏幸
  • Organizer: 日本生薬学会 第59年会
  • Place of Presentation: 千葉
  • Invited
• [Presentation] Calyculin生合成遺伝子クラスターの探索 (2012)
  • Author(s): 脇本敏幸
  • Organizer: 第７回 化学生態学研究会
  • Place of Presentation: 函館
  • Invited
• [Presentation] 海綿由来細胞毒性物質、カリクリンのAの生合成遺伝子クラスターの探索 (2012)
  • Author(s): 脇本敏幸、江上蓉子、阿部郁朗
  • Organizer: 日本薬学会第１３２年会(招待講演)
  • Place of Presentation: 北海道
• [Presentation] 海綿天然物Calyculin A生合成遺伝子クラスターのクローニング (2012)
  • Author(s): 江上蓉子、脇本敏幸、伊藤卓也、浅川義範、阿部郁朗
  • Organizer: 日本薬学会第１３２年会
  • Place of Presentation: 北海道
• [Presentation] 海綿内共生微生物由来の生物活性物質の探索研究 (2012)
  • Author(s): 竹重勇哉、Karen TAN、脇本敏幸、江上蓉子、阿部郁朗
  • Organizer: 日本薬学会第１３２年会
  • Place of Presentation: 北海道
• [Presentation] 海綿Discodermia calyx由来メタゲノムライブラリーからの抗菌活性化合物の単離 (2012)
  • Author(s): 賀蕊、江上蓉子，脇本敏幸，阿部郁朗
  • Organizer: 日本薬学会第１３２年会
  • Place of Presentation: 北海道
• [Presentation] Search for the biosynthetic gene cluster of the cytotoxic polyketide calyculin A from the marine sponge Discodermia calyx (2011)
  • Author(s): 脇本敏幸
  • Organizer: University of Bristol
  • Place of Presentation: University of Bristol (Bristol, UK)
  • Year and Date: 2011-11-22
• [Presentation] Search for the biosynthetic gene cluster of the cytotoxic polyketide calyculin A from the marine sponge Discodermia calyx (2011)
  • Author(s): 脇本敏幸
  • Place of Presentation: University of Bonn (Bonn, Germany)
  • Year and Date: 2011-11-22
• [Presentation] Search for the biosynthetic gene cluster of the cytotoxic polyketide calyculin A from the marine sponge Discodermia calyx (2011)
  • Author(s): 脇本敏幸
  • Place of Presentation: University of Tubingen (Tubingen, Germany)
  • Year and Date: 2011-10-27
• [Presentation] Chemistry and biology of calyculin A (2011)
  • Author(s): 脇本敏幸
  • Organizer: The 6th Korea-Japan Young Scientists Symposium
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2011-06-24
• [Presentation] 海綿Discordemia calyxに含まれる新規環状ペプチドcalyxamide Aの単離と構造決定 (2011)
  • Author(s): 木村美樹，脇本敏幸，阿部郁朗
  • Organizer: 日本生薬学会第５８回年会
  • Place of Presentation: 東京
• [Presentation] 海洋天然物Calyculin Aの蛍光標識 (2011)
  • Author(s): 但馬大紀，脇本敏幸，阿部郁朗
  • Organizer: 日本生薬学会第５８回年会
  • Place of Presentation: 東京
• [Presentation] 植物ポリケタイド合成酵素の合理的な酵素触媒機能の拡張による非天然型新規生理活性物質の創出 (2011)
  • Author(s): 森田洋行，森貴裕，山下誠，脇本敏幸，阿部郁朗
  • Organizer: 第５３回天然有機化合物討論会
  • Place of Presentation: 大阪
• [Presentation] Search for the biosynthetic gene cluster of the cytotoxic polyketide calyculin A from the marine sponge Discodermia calyx (2011)
  • Author(s): Toshiyuki Wakimoto
  • Organizer: University of Tubingen(招待講演)
  • Place of Presentation: Tubingen, Germany
• [Presentation] Search for the biosynthetic gene cluster of the cytotoxic polyketide calyculin A from the marine sponge Discodermia calyx (2011)
  • Author(s): Toshiyuki Wakimoto
  • Organizer: University of Bristol(招待講演)
  • Place of Presentation: Bristol, UK
• [Presentation] Search for the biosynthetic gene cluster of the cytotoxic polyketide calyculin A from the marine sponge Discodermia calyx (2011)
  • Author(s): Toshiyuki Wakimoto
  • Organizer: University of Bonn(招待講演)
  • Place of Presentation: Bonn, Germany
• [Remarks]
  • URL: http://www.f.u-tokyo.ac.jp/~tennen/head.htm