DEVELOPMENT OF A POTENT THROMBIN RECEPTOR-LIGAND

The N-terminal thrombin receptor peptide Leu-Leu-Arg-Asn-Pro-Asn-Asp-L ys-Tyr-Glu-Pro-Phe-OH (1) fully activates the thrombin receptor with a n EC(50) Of 10 mu M Structural features in the tetradecapeptide which are responsible for receptor activation have been elucidated. Agonist potency has been enhanced 1000-fold with the design of the shortened p eptide H-Ala-Phe(p-F)-Arg-Cha-HArg-Tyr-NH2 (56). This analog exhibits an EC(50) of 0.01 mu M and is the most potent agonist for receptor act ivation reported to date. The monoiodinated derivative H-Ala-Phe(p-F)- Arg-Cha-HArg-Tyr(3-I)-NH2 (59) exhibits an EC(50) of 0.03 mu M, a leve l sufficient for development of a radioligand.