Historical Aspects of Protein Synthesis *

DETERMINATION OF THE alpha peptide bond as the linkage mechanism joining amino acids into the long linear chain comprising the primary structure of the protein molecule provided the cornerstone for all subsequent work on the structure and synthesis of pr0teins.l In the early days of awareness of enzymes as biological catalysts there was a firmly fixed concept of the reversibility of their activity. It was considered that the same enzymes were involved in the synthesis as well as the degradation of proteins.2 In later pursuits of this possibility, Wastenys and Borsook3 found that concentrated partial hydrolysates of egg albumin would form “plasteins,” or large, protein-like masses, in the presence of pepsin or trypsin. Voegtlin and his colleagues4 also reported extensively that in the presence of sulfhydryl compounds and oxygen, soluble peptide-like components of ruptured cells precipitated out of solution readily, in what they considered to be conditions favoring resynthesis of proteins by intracellular proteolytic enzymes. In repeating these experiments, however, Linderstr$m-Lang and Johansen5 stated firmly that during this aeration of protein-proteinase digests no protein synthesis had taken place. In retrospect it would appear that in the case of Voegtlin’s experiments, disulfide cross linking of existing long peptide chains and aggregation of partial digests into insoluble products were taking place. The development of new methods for synthesizing synthetic peptide substrates by the Bergmann-Fruton Schoole made it possible to demonstrate that intracellular proteolytic enzymes had sharp specificities, and