title: Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library.
abstract: An encoded 13,020-member combinatorial library was synthesized containing a statine core. Evaluation of this library with plasmepsin II, an aspartyl protease required for hemoglobin metabolism in the malaria parasite, led to the identification of potent and selective inhibitors as well as novel structure-activity relationships.
authors.affiliation: Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Carroll
authors.forename: H
authors.initials: H
authors.lastname: Patel
authors.forename: T O
authors.initials: TO
authors.lastname: Johnson
authors.forename: T
authors.initials: T
authors.lastname: Guo
authors.forename: M
authors.initials: M
authors.lastname: Orlowski
authors.forename: Z M
authors.initials: ZM
authors.lastname: He
authors.forename: C L
authors.initials: CL
authors.lastname: Cavallaro
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: A
authors.initials: A
authors.lastname: Oksman
authors.forename: I Y
authors.initials: IY
authors.lastname: Gluzman
authors.forename: J
authors.initials: J
authors.lastname: Connelly
authors.forename: D
authors.initials: D
authors.lastname: Chelsky
authors.forename: D E
authors.initials: DE
authors.lastname: Goldberg
authors.forename: R E
authors.initials: RE
authors.lastname: Dolle
mesh_terms: D000596:Amino Acids; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D003001:Cloning, Molecular; D019992:Databases as Topic; D015195:Drug Design; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019151:Peptide Library; D010963:Plasmodium falciparum / Q000201:enzymology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015800:Protozoan Proteins; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000596:Amino Acids; D000962:Antimalarials; D006454:Hemoglobins; D009842:Oligopeptides; D019151:Peptide Library; D011480:Protease Inhibitors; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II; C013165:statine