- Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum.
Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum.
Journal of medicinal chemistry (2013-05-30)
Komagal Kannan Sivaraman, Alessandro Paiardini, Marcin Sieńczyk, Chiara Ruggeri, Christine A Oellig, John P Dalton, Peter J Scammells, Marcin Drag, Sheena McGowan
PMID23713488
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.
MATERIALS
Product Number
Brand
Product Description
Sigma-Aldrich
Leucine Aminopeptidase, microsomal from porcine kidney, Type IV-S, ammonium sulfate suspension, 10-40 units/mg protein (Bradford)
Sigma-Aldrich
Leucine Aminopeptidase, microsomal from porcine kidney, Type VI-S, lyophilized powder, ≥12 units/mg protein (biuret)
Sigma-Aldrich
L-Arginine, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%