Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library.
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.
Carroll
C D
CD
Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA.
Patel
H
H
Johnson
T O
TO
Guo
T
T
Orlowski
M
M
He
Z M
ZM
Cavallaro
C L
CL
Guo
J
J
Oksman
A
A
Gluzman
I Y
IY
Connelly
J
J
Chelsky
D
D
Goldberg
D E
DE
Dolle
R E
RE
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
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