Peptide modified gold-coated polyurethanes as thrombin scavenging surfaces

Thin layers of gold were deposited on polyurethane film and chemisorbed wit h three peptides having an N-terminal cysteine: Cys-Pro-Arg, Cys-(L)Phe-Pro -Arg, and Cys-(D)Phe-Pro-Arg. The ability of these surfaces to act. as thro mbin scavengers was evaluated. The peptides are related to the known thromb in inhibitor Phe-Pro-Arg chloromethyl ketone and were shown to have signifi cant thrombin inhibitory activity in solution. Attachment of the peptides t o gold was confirmed by water contact angle and X-ray photoelectron spectro scopy measurements. Thrombin adsorption from a buffer and plasma was invest igated, and chromogenic substrate assays were carried out for thrombin acti vity on the surfaces and in the supernatant following adsorption. The data suggest that the peptide-modified surfaces are able to adsorb thrombin with high affinity from a buffer and that thrombin is taken up selectively from plasma. The Cys-(D)Phe-Pro-Arg modified surfaces showed particularly high affinity for thrombin. It was also found that the activity of thrombin adso rbed on the peptide surfaces was inhibited, and inhibition was greatest on the Cys(D)Phe-Pro-Arg surface. We concluded that the peptide surfaces may h ave potential as antithrombogenic materials via their ability to scavenge a nd inhibit thrombin generated as a result of blood-material contact. (C) 20 00 John Wiley & Sons, Inc.