A peptide ligand of the human thrombin receptor antagonizes thrombin receptor activating peptide and α-thrombin-induced platelet aggregation

Structure and function studies on thrombin receptor activating peptide have revealed that certain residues in this peptide could be replaced with alanine. Attempts to prepare antagonist peptides by single amino acid modification of thrombin receptor activating peptide have not resulted in potent antagonist peptide. In the present study, we report an antagonist peptide with multiple alanine substitutions in both critical and non-critical residues. At a concentration of 32 mu M, this peptide could completely block agonist-induced platelet aggregation. The magnitude of the antagonist effect of this peptide depends on the concentration of the antagonist and preincubation time. This peptide blocked the platelet aggregation induced by the agonist peptide and also by a-thrombin, but did not have any effect on adenosine diphosphate or collagen-induced platelet aggregation indicating that the antagonist affects of this peptide may be pertained to thrombin receptor mediated events only. This peptide may be useful for blocking thrombin-mediated events like thrombosis and restenosis or can be used as a template for developing more efficient thrombin receptor antagonists. (C) Harcourt Publishers Ltd 2000.