Journal of medicinal and pharmaceutical chemistry 2013-06-27

Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum.

Komagal Kannan Sivaraman, Alessandro Paiardini, Marcin Sieńczyk, Chiara Ruggeri, Christine A Oellig, John P Dalton, Peter J Scammells, Marcin Drag, Sheena McGowan

Index: J. Med. Chem. 56(12) , 5213-7, (2013)

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Abstract

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-activity 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.