D-Phe-Pro-p-Amidinobenzylamine: A potent and highly selective thrombin inhibitor
β Scribed by Michael R. Wiley; Nickolay Y. Chirgadze; David K. Clawson; Trelia J. Craft; Donetta S. Gifford-Moore; Noel D. Jones; Jennifer L. Olkowski; Leonard C. Weir; Gerald F. Smith
- Publisher
- Elsevier Science
- Year
- 1996
- Tongue
- English
- Weight
- 303 KB
- Volume
- 6
- Category
- Article
- ISSN
- 0960-894X
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## Abstract The irreversible thrombin inhibitor DβPheβProβArgβchloromethylketone (PPACK) was covalently immobilized to PEGylated polymer thin films at its primary Ξ±βamino group. Activity assays and capture of radioconjugated thrombin reveal that the PPACKβdecorated surfaces could bind thrombin form
Removal of the [3-ketoamide functionality from L-370,518 (K~ = 0.09 nM) provided a 5 nM K i inhibitor of thrombin: L-371,912. Comparison of the enzyme-inhibitor crystal structures suggests a possible explanation for the relatively small change in affinity for thrombin. L-371,912 is selective for thr