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Maitz, M.F. ; Sperling, C. ; Werner, C.
Immobilization of the irreversible thrombin inhibitor D-Phe-Pro-Arg-chloromethylketone: A concept for hemocompatible surfaces?

The irreversible thrombin inhibitor D-Phe-Pro-Arg-chloromethylketone (PPACK) was covalently immobilized to PEGylated polymer thin films at its primary a-amino group. Activity assays and capture of radioconjugated thrombin reveal that the PPACK-decorated surfaces could bind thrombin forming up to 30% of a monolayer density. Back-calculation of this high thrombin-inhibiting capacity indicated that the surface immobilization of the inhibitor was still associated with more than two orders of magnitude of loss of activity; increasing activity was observed at higher surface densities. PPACK-containing polymer films almost duplicated the plasma coagulation time when compared with the reference substrate without inhibitor. In whole blood, however, the anticoagulant properties were below those previously found for benzamidine-type reversible thrombin inhibitors; in addition, the surface exhibited inflammatory properties. It is concluded that immobilized reversible thrombin inhibitors are more effective by passivating higher amounts of thrombin in a cooperative action with antithrombin III. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010

Source
Journal of Biomedical Materials Research Part A 94, 905-912

DOI
http://dx.doi.org/10.1002/jbm.a.32780

Published
August 2010
 
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