title: Search for substrate-based inhibitors fitting the S2' space of malarial aspartic protease plasmepsin II.
abstract: Plasmepsin (Plm) has been identified as an important target for the development of new antimalarial drugs, since its inhibition leads to the starvation of Plasmodium falciparum. A series of substrate-based dipeptide-type Plm II inhibitors containing the hydroxymethylcarbonyl isostere as a transition-state mimic were synthesized. The general design principle was provision of a conformationally restrained hydroxyl group (corresponding to the set residue at the P2' position in native substrates) and a bulky unit to fit the S2' pocket.
authors.affiliation: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan. kiso@mb.kyoto-phu.ac.jp
authors.forename: Aiko
authors.initials: A
authors.lastname: Kiso
authors.forename: Koushi
authors.initials: K
authors.lastname: Hidaka
authors.forename: Tooru
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Azin
authors.initials: A
authors.lastname: Nezami
authors.forename: Ernesto
authors.initials: E
authors.lastname: Freire
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000201:enzymology*; D015800:Protozoan Proteins; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D009842:Oligopeptides; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II