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001-es BibID:BIBFORM043571
Első szerző:Meiring, Muriel
Cím:In vitro effect of a thrombin inhibition peptide selected by phage display technology / Meiring Muriel S., Litthauer Derek, Hársfalvi Jolan, van Wyk Veronica, Badenhorst Philip N., Kotzé Harry F.
Dátum:2002
ISSN:0049-3848
Megjegyzések:A repeated selection of phages from a cyclic heptapeptide phage display library resulted in the enrichment of phages that bind to human alpha-thrombin. One clone of the binding phages that competed with PPACK for binding to thrombin and that had the best binding characteristics was chosen. The amino acid sequence of the peptide displayed on this phage was determined and a peptide with the sequence, Cys-Asn-Arg-Pro-Phe-Ile-Pro-Thr-Cys was synthesised. This peptide, thrombin-inhibiting peptide (TIP), is a full competitive inhibitor of thrombin with an inhibition constant (K(i)) of 0.4974 mM. It lengthened the thrombin time and inhibited thrombin-induced platelet activation and the platelet release reaction, both in a dose-dependent manner. It also reduced platelet adhesion onto a human microvascular endothelial matrix in the parallel plate flow chamber under both arterial and venous shear conditions. Thus, we have selected and synthesised a cyclic heptapeptide that competes with PPACK to bind to thrombin and that can be developed as a direct antithrombin.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Thrombin antagonists and inhibitors
Thrombin
Peptide library
Recombinant fusion proteins
Bacteriophage M13 genetics
Phage display system
Megjelenés:Thrombosis Research. - 107 : 6 (2002), p. 365-371. -
További szerzők:Litthauer, Derek Hársfalvi Jolán (1949-) (klinikai biokémikus) van Wyk, Veronika Badenhorst, Philip N. Kotzé, Harry F.
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