Discovery of Plasmodium vivaxN-Myristoyltransferase Inhibitors: Screening, Synthesis, and Structural Characterization of their Binding Mode

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• 作者：Victor Goncalves ; James A. Brannigan ; David Whalley ; Keith H. Ansell ; Barbara Saxty ; Anthony A. Holder ; Anthony J. Wilkinson ; Edward W. Tate ; Robin J. Leatherbarrow
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：April 12, 2012
• 年：2012
• 卷：55
• 期：7
• 页码：3578-3582
• 全文大小：284K
• 年卷期：v.55,no.7(April 12, 2012)
• ISSN：1520-4804

文摘

N-Myristoyltransferase (NMT) is a prospective drug target against parasitic protozoa. Herein we report the successful discovery of a series of Plasmodium vivax NMT inhibitors by high-throughput screening. A high-resolution crystal structure of the hit compound in complex with NMT was obtained, allowing understanding of its novel binding mode. A set of analogues was designed and tested to define the chemical groups relevant for activity and selectivity.