STRUCTURE OF INSULIN 



mechanism, but is unique for each protein in determining the 

 amino acid sequence and possesses in this respect a very high 

 degree of specificity. Such specificity is somewhat difficuk to 

 conceive. The mechanism must be able to distinguish not only 

 between a valine and an isoleucine residue, but also uniquely for 

 all the other amino acids. Few enzymes show such a high spec- 

 ificity, and unless the factors involved are very different from 

 those involved in enzyme action a one-stage mechanism for 

 protein synthesis would hardly be expected to give rise to a 

 protein of unique structure. A greater specificity may, however, 

 be expected from a multistage process where differences in 

 reaction rates become magnified through successive stages 

 (see ref. 5). Clearly the present results can provide little in- 

 formation about the mechanisms of protein syntheses, but 

 they do provide certain limitations on those who are speculating 

 on the subject. 



The determination of the structure of insulin raises the 

 possibility of similar studies on other proteins. From a con- 

 sideration of the end groups of a large number of proteins it 

 appears that the chains of insulin with 21 and 30 residues, re- 

 pectively, are uniquely short. Other simple proteins such as 

 ribonuclease, lysozyme, or hemoglobin contain chains of about 

 100 residues, whereas many have much longer chains. So the 

 question arises as to whether the methods used for insuHn will be 

 sufficient to elucidate the complete structure of these more com- 

 plex proteins, or whether entirely new methods will have to be 

 developed. In the chains of insulin there are several amino 

 acids that occur only once in the molecule and these greatly 

 help in deducing the structure. In a chain of 100 residues there 

 will be very few, if any, such residues, whereas many will occur 

 5 to 10 times. This will make it extremely difficult to interpret 

 the results obtained with nonspecific types of degradation, such 

 as acid or peptic hydrolysis, and it will be necessary to obtain a 

 greater number of longer peptides to provide a unique structure. 

 Not only do longer peptides exist in much more complex mix- 

 tures than smaller ones but also they are more difficult to 



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