Search

Die tegniek van faagblootlegging is gebruik om ’n sikliese heptapeptied te selekteer wat met weefselfaktor(WF) kompeteer vir binding aan stollingsfaktor VIIa. Die aminosuurvolgorde van die peptied is Cys-Ala- Trp-Pro-His-Thr-Pro-Asp-Cys (C-AWPHTPD-C) en dit verleng die protrombientyd (PT) op ’n konsentrasie-afhanklike wyse. Die peptied beperk plaatjieklewing aan beide menslike endoteelsel- en weefselfaktormatrikse in ’n vloeikamermodel onder arteriële vloeitoestande. Die peptied funksioneer as ’n volledig mededingende inhibeerder van faktor VIIa met ’n inhibisiekonstante (Ki) van 123,2 μM. In sy huidige vorm is die peptied waarskynlik nie sterk genoeg om verder as antitrombotiese middel ontwikkel te word nie, maar verskillende strategieë kan gevolg word om die werking daarvan te versterk. AbstractFunctional characterisation of a factor VIIa inhibiting peptide, IP-7 selected by phage display technology By using the technique of phage display, we selected a cyclic heptapeptide sequence Cys-Ala-Trp-Pro-His-Thr-Pro-Asp-Cys (C-AWPHTPD-C) that competes with tissue factor for binding to coagulation factor VII. This peptide prolongs the prothrombin time (PT) in a concentration dependent way. It also reduces platelet adhesion to both human endothelial cell and tissue factor matrixes in a flow chamber under arterial flow conditions. Furthermore, it acts as a full competitive inhibitor of factor VIIa with an inhibition constant (Ki) of 123,2 μM. In its current form the peptide is probably not sufficiently potent for development as an antithrombotic agent, but different strategies could be followed to reinforce its performance.