The design of potent, selective, non-covalent, peptide thrombin inhibitors utilizing imidazole as a S1 binding element.
Modeling of neutral or mildly basic functional groups in the S1 site of thrombin led to the targeting of imidazole as a S1 binding element and correctly predicted the optimal chain length for connecting this group with the S2 and S3 binding elements. Derivatives of 4-(3-aminopropyl)-imidazole can be selective inhibitors of thrombin demonstrating potent anticoagulant activity.
Wiley
M R
MR
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Weir
L C
LC
Briggs
S L
SL
Chirgadze
N Y
NY
Clawson
D
D
Gifford-Moore
D S
DS
Schacht
A L
AL
Smith
G F
GF
Vasudevan
V
V
Zornes
L L
LL
Klimkowski
V J
VJ
D000991:Antithrombins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D007093:Imidazoles / Q000378:metabolism*; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000991:Antithrombins; D007093:Imidazoles; D010455:Peptides