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An Unexpected Example of Protein-Templated Click Chemistry

Authors

  • Dr. Takayoshi Suzuki,

    1. Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603 (Japan), Fax: (+81) 52-836-3407
    2. PRESTO (Japan) Science and Technology Agency (JST), 4-1-8 Honcho Kawaguchi, Saitama 332-0012 (Japan)
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  • Yosuke Ota,

    1. Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603 (Japan), Fax: (+81) 52-836-3407
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  • Yuki Kasuya,

    1. Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603 (Japan), Fax: (+81) 52-836-3407
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  • Dr. Motoh Mutsuga,

    1. Division of Food Additives, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan)
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  • Dr. Yoko Kawamura,

    1. Division of Food Additives, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan)
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  • Dr. Hiroki Tsumoto,

    1. Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603 (Japan), Fax: (+81) 52-836-3407
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  • Dr. Hidehiko Nakagawa,

    1. Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603 (Japan), Fax: (+81) 52-836-3407
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  • Prof. M. G. Finn,

    1. Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-8850
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  • Prof. Naoki Miyata

    1. Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603 (Japan), Fax: (+81) 52-836-3407
    2. Division of Organic Chemistry, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan)
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  • This work was supported in part by the JST PRESTO program (T.S.) and grants from Taisho Pharmaceutical Co., Ltd. (T.S.), the Uehara Memorial Foundation (T.S.), and the Skaggs Institute for Chemical Biology (M.G.F.).

Abstract

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Mit einem Klick: Bei der Suche nach Histon-Desacetylase(HDAC)-Inhibitoren unter Anwendung der Klick-Chemie wurde das erste Beispiel für eine Protein-Kupfer-Beschleunigung der Azid-Alkin-Cycloaddition gefunden. Das Kupferzentrum in HDAC8 katalysiert die Triazolbildung zwischen einem Azid-Alkin-Paar unter 30 Möglichkeiten. Diese Befunde ebnen einen neuen Weg zu HDAC-Inhibitoren und neuartigen Protein-basierten Katalysatoren für die Klick-Chemie

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