Peptide modified gold-coated polyurethanes as thrombin scavenging surfaces.
Thin layers of gold were deposited on polyurethane film and chemisorbed with 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 thrombin scavengers was evaluated. The peptides are related to the known thrombin inhibitor Phe-Pro-Arg chloromethyl ketone and were shown to have significant thrombin inhibitory activity in solution. Attachment of the peptides to gold was confirmed by water contact angle and X-ray photoelectron spectroscopy measurements. Thrombin adsorption from a buffer and plasma was investigated, and chromogenic substrate assays were carried out for thrombin activity 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 adsorbed 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 have potential as antithrombogenic materials via their ability to scavenge and inhibit thrombin generated as a result of blood-material contact.
Sun
X
X
Department of Chemical Engineering, McMaster University, Hamilton, Ontario L8S 4L7, Canada.
Sheardown
H
H
Tengvall
P
P
Brash
J L
JL
D000327:Adsorption; D000990:Antithrombin III / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D007553:Isotope Labeling; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D011140:Polyurethanes / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry; D012996:Solutions; D013055:Spectrophotometry, Infrared; D013499:Surface Properties; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000737:chemistry*; D014961:X-Ray Diffraction
D007457:Iodine Radioisotopes; D010455:Peptides; D011140:Polyurethanes; D011506:Proteins; D012996:Solutions; D001710:Biotin; D006046:Gold; D000990:Antithrombin III; D005340:Fibrinogen; D013917:Thrombin