RATIONAL DESIGN OF SELECTIVE THROMBIN INHIBITORS

Authors
KIM S HWANG SY KIM YK YUN M OH YS
Citation
S. Kim et al., RATIONAL DESIGN OF SELECTIVE THROMBIN INHIBITORS, Bioorganic & medicinal chemistry letters, 7(7), 1997, pp. 769-774
Citations number
25
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
7
Issue
7
Year of publication
1997
Pages
769 - 774
Database
ISI
SICI code
0960-894X(1997)7:7<769:RDOSTI>2.0.ZU;2-W
Abstract
Thrombin inhibitors with functionalized benzamidines as surrogates for arginine were designed, synthesized, and characterized. Amino acid se quence difference in the position 190 between thrombin and trypsin was exploited in the design to enhance selectivity over trypsin. A repres entative compound 6 showed high potency (Ki of 45.5 nM) and extremely high specificity over trypsin (over 10,000 fold). (C) 1997 Elsevier Sc ience Ltd.