Structure-activity studies of the thrombin receptor activating peptide.

Cleavage of the human platelet thrombin receptor by thrombin exposes a new N-terminal which acts as a putative tethered ligand. A synthetic peptide--"SFLL" (SFLLRNPNDKYEPF), corresponding to the new N-terminal region, activates and induces platelet aggregation and serotonin secretion. We have found that the pentapeptide--SFLLR is the minimal peptide length which retains full activity in inducing [14C]serotonin secretion. Structure-activity relationship studies were performed on this pentameric peptide. Systematic replacement of all amino acids with L-Ala indicated the importance of F-2, L-3 and R-5 for activity. Further studies demonstrated that the positive charge at the N-terminus, but not at the C-terminus of the pentapeptide, is crucial for activity.