A NOVEL PEPTIDE MOTIF FOR PLATELET FIBRINOGEN RECEPTOR RECOGNITION

To develop a specific antagonist of platelet alpha IIb beta 3 using sm all linear peptides, we synthesized a series of hexapeptides that did not have an Arg-Gly-Asp (RGD) sequence and examined their anti-platele t activity and their specificity for alpha IIb beta 3, We found a nove l motif sequence, Pro-X1-X2-X3-Asp-X4, where X1 to X4 were all L-form alpha-amino acids, which specifically inhibited aggregation of human p latelets at submicromolar concentrations, The Pro residue at the N ter minus was essential to the anti-platelet activity, and the acetylation of the imino group of this residue also resulted in the complete loss of the activity, The results of the binding assay using purified huma n platelet alpha IIb beta 3 and placental, PQ and those of the cell ad hesion assay suggest that this motif peptide is highly specific for pl atelet alpha IIb beta 3 among other integrins. Flow cytometric studies using an fluorescein isothiocyanate-labeled RGD peptide showed that t his motif peptide inhibited the binding of an RGD peptide to activated platelets, suggesting that it has the same inhibitory mode as RGD pep tides, Conformational analysis of this motif peptide and an RGD-contai ning peptide suggests that the imino group of the Pro residue may subs titute for the role of the guanidino group of the Arg residue of the R GD sequence.