HYDROLYSIS OF PEPTIDE BONDS 



Finally it should be mentioned that recent years have witnessed 

 the discovery, in e\'er-increasing number, of proteolytic enzymes 

 adapted to the hydrolysis of peptides of rf-amino acids (3,25,29). The 

 existence of such enzymes presents us with an interesting problem: 

 if the antipodal specificity of a peptidase has its basis in the nature of 

 the essential center, then the essential center of a ^-peptidase should 

 possess a configuration antipodal to that of the corresponding /-pepti- 

 dase; cf. also Lettr6 (22). 



Role oj Proteolytic Enzymes in Peptide Synthesis 



In recent years, especial emphasis has been given to the dynamic 

 character of protein metabolism. The studies of Whipple (24), Schoen- 

 heimer (30), and others have given dramatic evidence for the view 

 that, in the tissues of animals and plants, protein molecules are rapidly 

 and continuously broken down and new protein molecules built up. 

 The recognition of the "dynamic equilibrium" of proteins in vivo has 

 brought to the fore the question of the nature of the enzymes that 

 selectively catalyze the sequences of chemical reactions in protein 

 synthesis and breakdown. More particularly, much attention has 

 been given to the nature of the enzymes that micdiate the synthesis of 

 peptide bonds between the individual amino acids. One view, which 

 is held \videly, is that the biosynthesis of peptide bonds is catalyzed 

 by the same enzymes that are responsible for the cleavage of peptide 

 bonds; in other words, biological peptide synthesis is thought to repre- 

 sent a reversal of the degradative action of the proteolytic enzymes. 

 The tissue proteolytic enzymes which are presumed to perform in vivo 

 synthesis are those frequently designated "cathepsins" (in the case of 

 animal tissues) and "papainases" (in the case of plant tissues). 



The view that the hydrolytic action of proteolytic enzymes 

 might be reversed was advanced by several workers at the start of the 

 century and was later championed by Wasteneys and Borsook (32). 

 More recently, it was shown unequivocally (7) that numerous proteo- 

 lytic enzymes can catalyze, in model experiments, the synthesis of 

 peptide bonds. One of many examples of such synthesis is the catalysis, 

 by activated papain, of the following reaction: benzoyl-Z-leucine + 

 /-leucinanilide -^ benzoyl-/-leucyl-/-leucinanilide. 



The fact that, in model experiments of this type, compoimds 

 of known and relatively simple structure are involved, in contrast to 



