Macrocyclic hexapeptide analogues of the thrombin receptor (PAR-1) activation motif SFLLRN

The thrombin receptor (PAR-1) is activated by α-thrombin to stimulate various cell types, including platelets, through the tethered-ligand sequence SFLLRN. Macrocyclic peptide analogues of SFLLRN were synthesized and evaluated in vitro. In general, the compounds were much less potent in inducing platelet aggregation relative to SFLLRN-NH2 and did not act as antagonists of α-thrombin. Derivative 3c was the most potent macrocycle in activating PAR-1, with an EC50 of 24 μM.