Can an antibody-combining site be mimicked synthetically? The possible surface simulation synthesis of two antibody-combining sites complementary to two antigenic sites of lysozyme.

Our recent determination of the complete antigenic structure of native lysozyme was made possible by our introduction of the "surface simulation" synthetic concept. The remarkable success afforded by this strategy in the synthetic construction of antigenic sites prompted us to investigate whether it can be applied to mimic antibody-combining sites. Two peptides, designed to be complementary to antigenic sites 2 and 3 of lysozyme, were synthesized and their immunochemistry was studied. Each of the two complementary peptides exhibited an appreciable inhibitory activity towards the reaction of lysozyme with its antisera. Peptide immunoadsorbents bound only lysozyme and not antibody or myoglobin. Neither of the two peptides had any immunochemical activity in the myoglobin or bovine serum albumin immune systems. Furthermore, it was shown that three control synthetic peptides of myoglobin, of similar charge but different sequence, had no inhibitory effect on the lysozyme immune reaction. The evidence indicates that the antibody-combining sites sgainst antigenic sites 2 and 3 of native lysozyme were successfully mimicked synthetically, at least in terms of binding function.