A SYNTHETIC PEPTIDE WITH ANTIPLATETLET ACTIVITY DERIVED FROM A CDR OFAN ANTI-GPIIB-IIIA ANTIBODY

A monoclonal antibody, AC7, directed against the RGD (Arg-Gly-Asp) bin ding site on the GpIIIa subunit of the platelet fibrinogen receptor, i nteracts only with activated platelet. In order to identify the region s of AC7 that interact with the receptor, cDNA sequences of AC7 immuno globulin heavy and light chain variable regions were determined. Among the six complementarity-determining regions (CDRs) of AC7, the CDR3 h eavy chain (H3) contains homology to the RGDF sequence within fibrinog en. A synthetic peptide encompassing the H3 region (H3, RQMIRGYFDV) in hibited platelet aggregation and fibrinogen binding to platelet (IC50 = 700 mu M). The inhibitory potencies of modified H3 peptides suggest that the RGYF sequence within the H3 peptide mimic the receptor recogn ition sequence in fibrinogen.