J. S. FRUTON 



^-tyrosylglycinamide (9). The hypothesis of the essential center 

 offers an explanation for such antipodal specificity. In order to act 



HO- 



-/ N— CH2 H H CH2— / V-OH 



^ ^ \ / \ / ^ ^ 



C G 



/\ < E /\ < E 



HN CO HN CO 



i I II 



OC NH OC NH 



/ \ / \ 



/-antipode (/-antipode 



Chymotrypsin 



I 



upon the substrate, the enzyme mast approach the substrate closely 

 so that the groups in the essential center of the enzyme can combine 

 with the indispensable groups in the backbone of the substrate. If we 

 consider the tetrahedral arrangement of the groups about the asym- 

 metric carbon atom, it becomes evident that the enzyme must approach 

 the substrate from the right side in order to combine with the essential 

 backbone groups of the substrate. In the case of benzoyl-af-tyrosyl- 

 glycinamide, the side chain prevents the enzyme from approaching the 

 backbone groups, and therefore the enzyme cannot split the substrate. 



When this theory of antipodal specificity was first proposed 

 (5), it was suggested that the size of the side chain of a'-alanine should 

 be sufficiently small so that the combination of the essential center of 

 the enzyme with the backbone groups of the substrate would not be 

 prevented completely, but would be made more difficult. This steric 

 hindrance should result in a retardation of the enzymic action on 

 peptides of (/-alanine as compared with its action on the /-form. In 

 fact, it was found that crystalline pancreatic carboxypeptidase was 

 able to hydrolyze carbobenzoxyglycyl-i^-alanine, albeit much more 

 slowly than the /-form (8). 



It must be emphasized that the above conclusion can be correct 

 only when it has been established that it is the same enzyme which 

 hydrolyzes the two substrates containing d- and /-alanine. This res- 

 ervation applies particularly to earlier experiments in which a study 

 was made of the antipodal specificity of so-called dipeptidase and of 

 aminopeptidase (12), since the existence of individual dipeptidases as 

 well as the homogeneity of "aminopeptidase" have become doubtful. 



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