title: Additional interaction of allophenylnorstatine-containing tripeptidomimetics with malarial aspartic protease plasmepsin II.
abstract: Based on a highly potent allophenylnorstatine-containing inhibitor, KNI-10006, against the plasmepsins of Plasmodium falciparum, we synthesized a series of tripeptide-type compounds with various N-terminal moieties and evaluated their inhibitory activities against plasmepsin II. Certain phenylacetyl derivatives exhibited extremely high affinity with K(i) values of less than 0.1n M suggesting successful hydrophobic interactions.
authors.affiliation: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Koushi
authors.initials: K
authors.lastname: Hidaka
authors.forename: Tooru
authors.initials: T
authors.lastname: Kimura
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tsuchiya
authors.forename: Mami
authors.initials: M
authors.lastname: Kamiya
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ruben
authors.forename: Ernesto
authors.initials: E
authors.lastname: Freire
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry* / Q000494:pharmacology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010654:Phenylbutyrates / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000201:enzymology*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D015800:Protozoan Proteins; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; C521559:KNI 10006; D009842:Oligopeptides; D010654:Phenylbutyrates; D011480:Protease Inhibitors; D015800:Protozoan Proteins; C034940:3-amino-2-hydroxy-4-phenylbutanoic acid; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II