天然物を基にした特異的かつ強力なキチナーゼ阻害剤の創製研究

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  • 廣瀬 友靖
    北里大学北里生命科学研究所 北里大学北里生命科学研究所大学院感染制御科学府

書誌事項

タイトル別名
  • Study on the Discovery of Novel Chitinase Inhibitors Based on Natural Products
  • テンネンブツ オ モト ニ シタ トクイテキ カツ キョウリョク ナ キチナーゼ ソガイザイ ノ ソウセイ ケンキュウ

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説明

  Chitin, the second most abundant polysaccharide in nature, is a constituent of fungal cell walls, the exoskeletons of crustaceans and insects and the microfilarial sheaths of parasitic nematodes. Chitin has, so far, not been found in mammals. Accumulation of chitin by organisms is modulated by chitin synthase-mediated biosynthesis and by chitinase-mediated hydrolytic degradation. Thus, chitinases are expected to be specific targets for antifungal, insecticidal and antiparasitic agents. Paradoxically, while chitin does not exist in mammals, human chitinase family members, such as acidic mammalian chitinase, have recently been described, and offer significant potential for the treatment of asthma and other related diseases in humans. This review covers the development of two chitinase inhibitors of natural origin, Argifin and Argadin, isolated from the cultured broth of microorganisms in our laboratory. In particular, the practical total synthesis of these natural products and discovery methods that generate only highly-active compounds using a kinetic target (chitinase)-guided synthesis approach (termed in situ click chemistry) are described.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 132 (9), 1001-1010, 2012-09-01

    公益社団法人 日本薬学会

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