Development of a Potent Thrombin Receptor Ligand

Article abstract of DOI:10.1021/jm00020a029

The N-terminal thrombin receptor peptide H-Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe-OH (1) fully activates the thrombin receptor with an EC50 of 10 μM.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 peptide H-Ala-Phe(p-F)-Arg-Cha-HArg-Tyr-NH2 (56).This analog exhibits an EC50 of 0,01 μM and is the most potent agonist for receptor activation reported to date.The monoiodinated derivative H-Ala-Phe(p-F)-Arg-Cha-HArg-Tyr(3-I)-NH2 (59) exhibits an EC50 of 0.03 μM, a level sufficient for development of a radioligand.