ANTIGENICITY OF TOPOCHEMICALLY RELATED PEPTIDES

Antibodies raised in rabbits against multimeric all-L peptides (MAP's) were first made monospecific by affinity chromatography on immobilize d antigen columns and then tested for their ability to cross-react wit h topologically related variants of the parent antigen, where the chir ality of each amino-acid residue (inverse derivatives), or the peptide sequence orientation (retro derivatives), was inverted, or where both modifications were simultaneously introduced (retro-inverso derivativ es). Retro, inverse, and retro-inverso forms of the parent peptide wer e prepared, both in the linear as well as in the BSA-conjugated form, and found to cross-react to a significant extent with affinity purifie d polyclonal antibodies raised against the parent peptide. Peptide var iants displayed similar dose-dependent inhibitory effects on the inter action between immobilized parent antigen and affinity purified antibo dies. Analysis of molecular models of the peptide variants in the tran s-configuration suggested that the topological equivalence of alternat ing side chains in the series of related peptides may be responsible f or the observed cross-recognition, leading to the formation of similar recognition surfaces which could mimic the parent peptide antigenic s tructure.