Inhibition of platelet adhesion by peptidomimetics mimicking the interactive β-hairpin of glycoprotein Ibα

The design and evaluation of a series of cyclic peptides inhibiting platelet adhesion are described. β-Hairpin peptidomimetics mimicking the interaction sites of the platelet receptor glycoprotein (GP)Ibα with von Willebrand factor (vWF) were synthesised and evaluated for their ability to increase platelet velocity under high shear conditions and to inhibit shear-induced platelet aggregation. A cyclic and bridged dodecapeptide 2e containing a heterochiral diproline motif was identified as a lead compound for the generation of a novel class of potential antiplatelet agents.