title: Synthesis and structure-activity relationships of phosphonic arginine mimetics as inhibitors of the M1 and M17 aminopeptidases from Plasmodium falciparum.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton Campus, Melbourne, VIC 3800, Australia.
authors.forename: Komagal
authors.initials: K
authors.lastname: Kannan Sivaraman
authors.forename: Alessandro
authors.initials: A
authors.lastname: Paiardini
authors.forename: Marcin
authors.initials: M
authors.lastname: Sieńczyk
authors.forename: Chiara
authors.initials: C
authors.lastname: Ruggeri
authors.forename: Christine A
authors.initials: CA
authors.lastname: Oellig
authors.forename: John P
authors.initials: JP
authors.lastname: Dalton
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Scammells
authors.forename: Marcin
authors.initials: M
authors.lastname: Drag
authors.forename: Sheena
authors.initials: S
authors.lastname: McGowan
mesh_terms: D001120:Arginine / Q000737:chemistry*; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018826:CD13 Antigens / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D010757:Phosphorous Acids / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000201:enzymology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D010757:Phosphorous Acids; C570063:phosphonic acid; D001120:Arginine; D018826:CD13 Antigens