Title of article :
The design of potent, selective, non-covalent, peptide thrombin inhibitors utilizing imidazole as a S1 binding element
Author/Authors :
Michael R. Wiley، نويسنده , , Leonard C. Weir، نويسنده , , Steven L. Briggs، نويسنده , , Nickolay Y. Chirgadze، نويسنده , , David Clawson، نويسنده , , Donetta S. Gifford-Moore، نويسنده , , Aaron L. Schacht، نويسنده , , Gerald F. Smith، نويسنده , , Vasu Vasudevan، نويسنده , , Larry L. Zornes، نويسنده , , Valentine J. Klimkowski، نويسنده ,
Abstract :
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.
