Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, VIC 3800, Australia.
J Med Chem. 2013 Jun 27;56(12):5213-7. doi: 10.1021/jm4005972. Epub 2013 Jun 13.
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.
疟原虫 Plasmodium falciparum 利用两种金属氨肽酶，PfA-M1 和 PfA-M17，这对寄生虫的生存至关重要。抑制这两种酶中任何一种酶活性的化合物都是开发新抗疟药物的先导化合物。在这里，我们报告了一小部分膦酸精氨酸类似物的合成和构效关系研究，这些化合物可以探测两种酶的 S1 口袋，并确定对双重抑制剂很重要的必需相互作用。
