Precise determination of protein antigenic structures has unravelled the molecular immune recognition of proteins and provided a prototype for synthetic mimicking of other protein binding sites.

Intensive research in the author's laboratory had culminated in the determination and synthesis of all the antigenic sites of myoglobin in 1975 and of lysozyme in 1978. Very recently most of the antigenic sites of serum albumin were also localized and synthesized. These investigations provided the first unique insight into the molecular features responsible for the immune recognition of protein antigens and of the factors which determine and regulate the antigenicity of the sites. But moreover, these studies have charted a multi-approach chemical strategy for investigation and synthetic duplication of protein binding sites. Furthermore, the concept of 'surface-simulation' synthesis, which we introduced and developed during our determination of the antigenic structure of lysozyme, has provided a remarkable dimension of unlimited versatility for the synthetic mimicking of any type of protein binding sites. In this concept, the spatially adjacent residues of a protein binding site are linked directly via peptide bonds with appropriate spacers into a single peptide which does not exist in the protein but mimicks a surface region of it. This has proved to be a powerful concept in protein molecular recognition and has opened up many untapped avenues in investigation, duplication and perhaps manipulation of a variety of protein activities. In fact, binding sites representing other protein activities (including antibody combining sites) have or are now being mimicked synthetically in our laboratory by the concept of surface-simulation synthesis.