The design of potent, selective, non-covalent, peptide thrombin inhibitorsutilizing imidazole as a S1 binding element

Authors
Wiley, MR Weir, LC Briggs, SI Chirgadze, NY Clawson, D Gifford-Moore, DS Schacht, AL Smith, GF Vasudevan, V Zornes, LL Klimkowski, VJ
Citation
Mr. Wiley et al., The design of potent, selective, non-covalent, peptide thrombin inhibitorsutilizing imidazole as a S1 binding element, BIOORG MED, 9(18), 1999, pp. 2767-2772
Citations number
14
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
9
Issue
18
Year of publication
1999
Pages
2767 - 2772
Database
ISI
SICI code
0960-894X(19990920)9:18<2767:TDOPSN>2.0.ZU;2-J
Abstract
Modeling of neutral or mildly basic functional groups in the S1 site of thr ombin led to the targeting of imidazole as a S1 binding element and correct ly 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 activi ty. (C) 1999 Elsevier Science Ltd. All rights reserved.