Synthesis and Structure鈥揂ctivity Relationships of Phosphonic Arginine Mimetics as Inhibitors of the M1 and M17 Aminopeptidases from Plasmodium falciparum

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• 作者：Komagal Kannan Sivaraman ; Alessandro Paiardini ; Marcin Sie艅czyk ; Chiara Ruggeri ; Christine A. Oellig ; John P. Dalton ; Peter J. Scammells ; Marcin Drag ; Sheena McGowan
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：June 27, 2013
• 年：2013
• 卷：56
• 期：12
• 页码：5213-5217
• 全文大小：250K
• 年卷期：v.56,no.12(June 27, 2013)
• ISSN：1520-4804

文摘

The malaria parasite Plasmodium falciparum employs two metallo-aminopeptidases, PfA-M1 and PfA-M17, which are essential for parasite survival. Compounds that inhibit the activity of either enzyme represent leads for the development of new antimalarial drugs. Here we report the synthesis and structure鈥揳ctivity relationships of a small library of phosphonic acid arginine mimetics that probe the S1 pocket of both enzymes and map the necessary interactions that would be important for a dual inhibitor.