A novel molecular design of thrombin receptor antagonist

In a computer modeling of transmembrane domains of human thrombin receptor, Lys-158 was found near the ligand binding site. To capture this basic residue, analogs of peptide ligand containing a series of acidic amino acids were synthesized and assayed for human platelet aggregation, and Ser-( p-F)Phe-Aad(= α-aminoadipic acid)-Leu-Arg-Asn-Pro-NH 2 was found to be a potent antagonist. In a computer modeling of transmembrane domains of human thrombin receptor, Lys-158 was found near the ligand binding site. To capture this basic residue, analogs of peptide ligand containing a series of acidic amino acids were synthesized and assayed for human platelet aggregation, and Ser-( p-F)Phe-Aad(= α-aminoadipic acid)-Leu-Arg-Asn-Pro-NH 2 was found to be a potent antagonist.