Evaluation of a structure-based statine cyclic diamino amide encoded combinatorial library against plasmepsin II and cathepsin D.
A structure-based 18,900-member combinatorial library was synthesized containing a statine template and three cyclic diamino acids as potential P1, P2-P4 surrogates. Evaluation of this encoded library against two aspartyl proteases, plasmepsin II and cathepsin D, led to the identification of selective inhibitors for each enzyme.
Carroll
C D
CD
Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08543, USA.
Johnson
T O
TO
Tao
S
S
Lauri
G
G
Orlowski
M
M
Gluzman
I Y
IY
Goldberg
D E
DE
Dolle
R E
RE
D000577:Amides / Q000494:pharmacology*; D000596:Amino Acids / Q000494:pharmacology*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002402:Cathepsin D / Q000037:antagonists & inhibitors*; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology*; D015800:Protozoan Proteins; D013329:Structure-Activity Relationship
D000577:Amides; D000596:Amino Acids; D011480:Protease Inhibitors; D015800:Protozoan Proteins; D016282:Aspartic Acid Endopeptidases; C100637:plasmepsin II; D002402:Cathepsin D; C013165:statine