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

The thrombin receptor (PAR-1) is activated by alpha-thrombin to stimulate v arious cell types, including platelets, through the tethered-ligand sequenc e SFLLRN. Macrocyclic peptide analogues of SFLLRN were synthesized and eval uated 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 alpha-thrombin. Derivative 3c was the most potent macrocycle in activat ing PAR-1, with an EC50 of 24 mu M. (C) 1999 Elsevier Science Ltd. All righ ts reserved.