Exploration of Innate Immune Regulators from Unexploited Microorganisms

• Project/Area Number: 23710247
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Living organism molecular science
• Research Institution: Tohoku University
• Principal Investigator: KIKUCHI Haruhisa 東北大学, 大学院・薬学研究科, 准教授 (90302166)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 天然物化学 / 自然免疫 / 二次代謝産物 / 生物活性物質 / 未利用微生物 / 天然物有機化学

Research Abstract

To screen pharmaceuticals that target innate immunity, we established an ex vivo culture system based on the innate immune response of Drosophila, which is highly useful for identifying immune regulators that act on human innate immunity. We used this system to search for natural substances that regulate innate immunity, and identified terresterol and TM-DIF-1 as an activator and a suppressor, respectively. In addition, we synthesized gonytolide A, aspergillicin F and their derivatives.

Research Products

• [Journal Article] Chlorinated Dibenzofurans Isolated from the Cellular Slime Mold, Polysphondylium filamentosum, and Their Biological Activities (2013)
  • Author(s): Kikuchi, H.; Kubohara, Y.; Nguyen, V. H.; Katou, Y.; Oshima, Y. Novel
  • Journal Title: Bioorg. Med. Chem Volume: (In press) Issue: 15 Pages: 4628-4633
  • DOI: 10.1016/j.bmc.2013.05.022
  • Peer Reviewed
• [Journal Article] Terresterol, a Polyoxygenated Lanostanoid, Isolated from the Oomycete Saprolegnia terrestris, and Its Innate Immune-Promoting Activity (2013)
  • Author(s): Kikuchi, H., Sato, Y., Kurata, S., Katou, Y., Oshima, Y.
  • Journal Title: Tetrahedron Volume: 69 Issue: 17 Pages: 3536-3542
  • DOI: 10.1016/j.tet.2013.02.088
  • Peer Reviewed
• [Journal Article] Isolation, Synthesis and Biological Activity of Biphenyl and m-Terphenyl-Type Compounds from Dictyostelium Cellular Slime Molds (2012)
  • Author(s): Kikuchi, H.; Matsuo, Y.; Katou, Y.; Kubohara, Y.; Oshima, Y
  • Journal Title: Tetrahedron Volume: 68 Issue: 43 Pages: 8884-8889
  • DOI: 10.1016/j.tet.2012.08.041
  • Peer Reviewed
• [Journal Article] New Dimeric and Monomeric Chromanones, Gonytolides D-G, Isolated from the Fungus Gonytrichum sp (2012)
  • Author(s): Kikuchi, H., Isobe, M., Kurata, S., Katou, Y., Oshima, Y.
  • Journal Title: Tetrahedron Volume: 68 Issue: 31 Pages: 6218-6223
  • DOI: 10.1016/j.tet.2012.05.064
  • Peer Reviewed
• [Journal Article] A phytoceramide analog stimulates the production of chemokines through CREB activation in human endothelial cells (2011)
  • Author(s): Sekiya, M.; Ueda, K.; Okazaki, K.; Terashima, J.; Katou, Y.; Kikuchi, H.; Kurata, S.; Oshima, Y
  • Journal Title: Int. Immunopharmacol Volume: 11 Issue: 10 Pages: 1497-1503
  • DOI: 10.1016/j.intimp.2011.05.001
  • Peer Reviewed
• [Journal Article] Revised Structure and Synthesis of Celastramycin A, a Potent Innate Immune Suppressor (2009)
  • Author(s): Kikuchi, H., Sekiya, M., Katou, Y., Ueda, K., Kabeya, T., Kurata, S., and Oshima, Y.
  • Journal Title: Organic letters Volume: 11 Issue: 17 Pages: 1693-1695
  • DOI: 10.1021/ol2018449
  • Peer Reviewed
• [Presentation] 未利用微生物・細胞性粘菌由来化合物からの自然免疫制御物質の探索 (2013)
  • Author(s): グウェンバンハイ,菊地晴久,倉田祥一朗,加藤泰弘,大島吉輝
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2013-03-29
• [Presentation] 自然免疫抑制物質celastramycin Aの作用分子メカニズムの解析 (2013)
  • Author(s): 佐久間直之,加藤泰弘,壁谷尚宏,倉田祥一朗,菊地晴久,大島吉輝
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2013-03-28
• [Presentation] 天然資源より得られた自然免疫増強物質の誘導体合成と生物活性 (2012)
  • Author(s): 星川毅,菊地晴久,阿部由布子,藤村信平,倉田祥一朗,大島吉輝
  • Organizer: 第30回メディシナルケミストリーシンポジウム
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2012-11-29
• [Presentation] Biologically Active Compounds Isolated from Unexploited Microorganisms (2012)
  • Author(s): Haruhisa Kikuchi
  • Organizer: International Symposium of Pharmaceutical Sciences
  • Place of Presentation: Soochow University (中国・蘇州市)(招待講演)
  • Year and Date: 2012-05-26
• [Presentation] 自然免疫増強物質gonytolide Aの誘導体合成と生物活性 (2012)
  • Author(s): 星川毅,菊地晴久,阿部由布子,倉田祥一朗,大島吉輝
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 北海道大学(札幌)
  • Year and Date: 2012-03-29
• [Presentation] 天然資源より得られた自然免疫増強物質の誘導体合成と生物活性 (2012)
  • Author(s): 星川毅，菊地晴久，阿部由布子，藤村信平，倉田祥一朗，加藤泰弘，大島吉輝
  • Organizer: 第30回メディシナルケミストリーシンポジウム
  • Place of Presentation: タワーホール船堀（東京都）
• [Presentation] Biologically Active Compounds Isolated from Unexploited Microorganisms (2012)
  • Author(s): Haruhisa Kikuchi
  • Organizer: International Symposium of Pharmaceutical Sciences
  • Place of Presentation: Soochow University (China)
  • Invited
• [Presentation] Yoshiteru Oshima Exploration of Innate Immune Regulators from Natural Resources (2011)
  • Author(s): Haruhisa Kikuchi, Mizuki Sekiya, YasuhiroKatou, Shoichiro Kurata
  • Organizer: AIMECS2011
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2011-11-30
• [Presentation] 環状デプシペプチドaspergillicin Eの自然免疫応答抑制作用とその合成研究 (2011)
  • Author(s): 藤村信平,菊地晴久,中村哲也,倉田祥一朗,加藤泰弘,大島吉輝
  • Organizer: 第50回記念日本薬学会東北支部大会
  • Place of Presentation: 東北薬科大学(仙台)
  • Year and Date: 2011-10-30
• [Presentation] Exploration of Innate Immune Regulators from Natural Resources (2011)
  • Author(s): Haruhisa Kikuchi, Mizuki Sekiya, Yasuhiro Katou, Shoichiro Kurata, Yoshiteru Oshima
  • Organizer: AIMECS2011
  • Place of Presentation: 東京
• [Presentation] 環状デプシペプチド aspergillicin E の自然免疫応答抑制作用とその合成研究 (2011)
  • Author(s): 藤村信平, 菊地晴久，中村哲也，倉田祥一朗，加藤泰弘，大島吉輝
  • Organizer: 第50回記念日本薬学会東北支部大会
  • Place of Presentation: 仙台