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.
Sabo
T
T
Israel Institute for Biological Research, Ness-Ziona.
Gurwitz
D
D
Motola
L
L
Brodt
P
P
Barak
R
R
Elhanaty
E
E
D000595:Amino Acid Sequence; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018179:Receptors, Thrombin; D012701:Serotonin / Q000097:blood; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000378:metabolism*
D009842:Oligopeptides; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D012701:Serotonin; D013917:Thrombin