A new ligand for immunoglobulin G subdomains by screening of a synthetic peptide library

By screening a synthetic peptide library of general formula (NH2-Cys1-X2-X3-X4)2-Lys-Gly-OH, a disulfide-bridged cyclic peptide, where X2-X3-X4 is the tripeptide Phe-His-His, has been selected as a ligand for IgG. The peptide, after a preliminary chromatog. characterization, has proved useful as a new affinity ligand for the purifn. of polyclonal as well as monoclonal antibodies from biol. fluids, with recovery yields of up to 90% (90% purity). The ligand is able to bind antibody fragments contg. both Fab and Fc from different antibody isotypes, a fact suggesting the presence of at least two different antibody-binding sites. While the recognition site on Fab is unknown, comparative binding studies with Fc, in assocn. with the striking similarities of the peptide (named Fc-receptor mimetic, FcRM) with a region of the human Fcƒ×RIII receptor, strongly indicate that the peptide could recognize a short amino acid stretch of the lower hinge region, which has a key role in autoimmune disease triggering. The unique properties make the ligand attractive for both the purifn. of antibody fragments and as a lead for the generation of Fc-receptor antagonists.