Putative binding sites in a platelet thrombin receptor (PAR-1) for the activating
peptide SFLLRNPNDKYEPF (AP) and for the bradykinin analogue MKRPPGFSPFRSSRIG were
revealed using a computer program for identifying complementary peptide segments.
The program is based on the assumption that interactions of agonist’s peptides and
protein’s receptors can be elucidated by complementary average hydropathies as much
as possible equal by size and opposite by sign. Some of the computer-found putative
binding sites were close to the supposed AP-PAR-1 contacts in the amino-terminal exodomain
and in the second extracellulary loop of PAR-1. Peptides complementary to these binding
sites were also computer-designed and were synthesized. They mostly inhibited the
aggregation of gel filtered platelets by thrombin (0.025 U/mL) with IC50 in a high micromolar range of concentrations. The peptide complementary to site L258-Y269
of PAR-1 induced aggregation of gel filtered platelets with EC50 = 98 [µmol/L] related to thrombin (0.025 U/mL) aggregation response.
Keywords
Hydropathic complementarity - thrombin receptor
