10 A Potent Chitinase Inhibitor, Argifin; An Effective Solid Phase Total Synthesis, and Creation of Novel Chitinase Inhibitor via Molecule Design and in situ Click Chemistry(Oral Presentation)
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- Sunazuka Toshiaki
- The Kitasato Institute, Kitasato University Center for Basic Research:Kitasato Institute for Life Science, Kitasato University
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- Hirose Tomoyasu
- The Kitasato Institute, Kitasato University Center for Basic Research
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- Sugawara Akihiro
- Kitasato Institute for Life Science, Kitasato University
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- Iguchi Kanami
- Kitasato Institute for Life Science, Kitasato University
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- Endo Ayako
- Kitasato Institute for Life Science, Kitasato University
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- Saito Yoshifumi
- Kitasato Institute for Life Science, Kitasato University
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- Yamamoto Tsuyoshi
- The Kitasato Institute, Kitasato University Center for Basic Research
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- Ui Hideaki
- Kitasato Institute for Life Science, Kitasato University
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- Gouda Hiroaki
- School of Pharmaceutical Sciences, Kitasato University
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- Hirono Shuichi
- School of Pharmaceutical Sciences, Kitasato University
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- Shiomi Kazuro
- Kitasato Institute for Life Science, Kitasato University
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- Watanabe Takeshi
- Department of Applied Biological Chemistry Faculty of Agriculture, Niigata University
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- Sharpless K. Barry
- The Scripps Research Institute
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- Omura Satoshi
- The Kitasato Institute, Kitasato University Center for Basic Research:Kitasato Institute for Life Science, Kitasato University
Bibliographic Information
- Other Title
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- 10 キチナーゼ阻害剤Argifinの固相全合成と分子設計、in situクリックケミストリーを駆使した新規キチナーゼ阻害剤の創製(口頭発表の部)
Abstract
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. Accumulation of chitin by organisms is modulated by chitin synthase-mediated biosynthesis and by chitinases-mediated hydrolytic degradation. Consequently, chitinases have been expected to be specific target for antifungal, insecticidal and antiparasitic agents. Argifin (1) represents a family of peptide products, of natural microorganic origin, isolated from the cultured broth of a fungal strain, Gliocladium sp. FTD-0668, by our research group and characterized as a novel chitinase inhibitor, with strong inhibitory activity against Serratia marcescens chitinases (SmChi). Recently, X-ray crystallographic analysis of chitinases-argifin complexes has revealed that there are strong hydrogen-bond interactions between the N^ω-methylcarbamoyl-L-arginine moiety and the motif of the hydrolytic pocket of bacterial chitinases, resulting in nanomolar to micromolar range inhibition. We report the efficient solid phase total synthesis of arigifin, the molecular design of novel chitinase inhibitors derived from its structure, and application of in situ click chemistry, using an azide-bearing simplified analogue, to identify more potent chitinase inhibitors.
Journal
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- Symposium on the Chemistry of Natural Products, symposium papers
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Symposium on the Chemistry of Natural Products, symposium papers 50 (0), 83-88, 2008
Symposium on the Chemistry of Natural Products Steering Committee
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Details 詳細情報について
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- CRID
- 1390001206078261888
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- NII Article ID
- 110007066770
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- ISSN
- 24331856
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- Text Lang
- ja
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- Data Source
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- JaLC
- CiNii Articles
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- Abstract License Flag
- Disallowed
