Creation of Novel Anti-allergic Leads Based on the Inhibition for Expression of IgE Receptors

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790109
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: Tohoku University
• Principal Investigator: TAMURA Satoru 東北大学, 理学(系)研究科(研究院), 講師 (30362619)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 抗アレルギー / IgEレセプター / マスト細胞 / chlorin e6 / RBL 2H3 / pheophorbide a / PCA反応

Research Abstract

Allergy is caused by chemical mediators degranulated from mast cells. This degranulation is derived through the important two steps. In a first step, immunoglobulin Es (IgEs) are attached on the IgE receptors on the surface of mast cells. Then, the IgEs on mast cells react with invaded allergens in a second step. In this circumstance, I wondered that the decrease of IgE receptors on the mast cells may be able to suppress allergic reactions. Based on this idea, I established the assay system for evaluation of the amount of IgE receptors on the surface of cultured mast cells by immunofluorescence staining and flow cytometry. By the screening from medicinal plants for inhibitors against expression of IgE receptors, chlorin e6 was found as a potent inhibitor. Fortunately, chlorin e6 suppressed the expression of IgE receptors not only in vitro but also in vivo rat experiments. Finally, chlorin e6 was clarified to inhibit in vivo allergic reaction of rats through po administration.

Research Products

• [Journal Article] Synthetic Studies of Cortistatin A Analogue from the CD-Ring Fragment of Vitamin D2 (2013)
  • Author(s): Kotoku, N.; Mizushima, K.; Tamura, S.; Kobayashi, M
  • Journal Title: Chem Pharm. Bull Volume: 61 Pages: 1024-1029
  • DOI: 10.1248/cpb.c13-00375
  • Peer Reviewed
• [Journal Article] Contribution of cage-shaped structure of physalins to their mode of action in inhibition of NF-κB activation (2013)
  • Author(s): Ozawa, M.; Morita, M.; Hirai, G.; Tamura, S.; Kawai, M.; Tsuchiya, A.; Oonuma, K.; Maruoka, K.; Sodeoka, M
  • Journal Title: ACS Med Chem. Lett Volume: 4 Pages: 730-735
  • DOI: 10.1021/ml400144e
  • Peer Reviewed
• [Journal Article] Triazoyl-phenyl linker system enhancing the aqueous solubility of a molecular probe and its affinity labeling of a target protein for jasmonate glucoside (2013)
  • Author(s): Tamura, S.; Inomata, S.; Ebine, M.; Genji, T.; Iwakura, I.; Mukai, M.; Shoji, M.; Sugai, T.; Ueda, M
  • Journal Title: Bioorg. Med. Chem. Lett Volume: 23 Pages: 188-193
  • DOI: 10.1016/j.bmcl.2012.10.124.
  • Peer Reviewed
• [Journal Article] Creation of readily accessible and orally active analogue of cortistatin A (2012)
  • Author(s): Kotoku, N.; Sumii, Y.; Hayashi, T, Tamura, .; Kawachi, T.; Shiomura, S.; Arai, M.; Kobayashi, M
  • Journal Title: ACS Med Chem. Lett Volume: 3(8) Pages: 673-677
  • DOI: 10.1021/ml300143d.
  • Peer Reviewed
• [Journal Article] Hybrid stereoisomers of a compact molecular probe based on a jasmonic acid glucoside : Syntheses and biological evaluations (2012)
  • Author(s): Ueda, M.; Yang, G.; Ishimaru, Y.; Itabashi, .; Tamura, S.; Kiyota, H.; Kuwahara, S.; Inomata, S.; Shoji, M.; Sugai, T
  • Journal Title: Bioorg. Med. Chem Volume: 20 Pages: 5832-5843
  • DOI: 10.1016/j.bmc.2012.08.003.
  • Peer Reviewed
• [Presentation] 天然物からメディシナルケミストリーとケミカルバイオロジー (2013)
  • Author(s): 田村理
  • Organizer: 第48回天然物化学談話会
  • Place of Presentation: 大津市
  • Year and Date: 2013-07-03
• [Book] 化学工業 (2014)
  • Author(s): 田村理
  • Total Pages: 15-21
  • Publisher: 化学工業社