THE SYNTHESIS OF THE PROTEINS 35 



The Structure of the Polypeptides and Diketopiperazines. 



From the methods by which the polypeptides are obtained by 

 synthesis it can only be concluded that their constituent amino acids 

 are combined together in the form of acid amides ; this method of 

 combination also occurs in the case of the oxyamino acids, e.g., leucyl- 

 isoserine, where the ester method of combination was excluded by special 

 investigations. The question of their structure, however, still remains 

 very complex, if the controversy concerning the structure of the amides 

 and amino acids, which has not yet been settled, be taken into account. 

 There is the possibility of lactam and lactim forms and of the free 

 amino acid and intramolecular salt; these are illustrated by the four 

 formulae for glycyl-glycine : 



NH, . CH 3 . CO NH . CH 2 . COOH NH a . CH 2 . C(OH)=N . CH 2 . COOH 



NH 3 . CH 2 . CO NH . CH 2 . COO NH 3 . CH a . C(OH)=N . CH 2 . COO 



For the sake of simplicity and since his observations have as yet led 

 to no choice between the above formulae, Fischer has adopted the first 

 formula, but in certain of the polypeptides the observations suggest 

 different structures, which will increase with the investigations upon the 

 more complex polypeptides, thus leucyl-diglycyl-glycine in its amor- 

 phous state is easily soluble in alcohol ; if the alcohol solution be 

 warmed on the water bath, the crystalline tetrapeptide commences to 

 separate out and in this state it is insoluble in alcohol. 



The carbethoxyl derivatives show another kind of isomerism ; car- 

 bethoxyl glycyl-glycine ester, when saponified by alkali, yielded glycyl- 

 glycyl carboxylic acid HOOC . NH . CH 2 . CO . NH . CH 2 . COOH ; 

 this compound on esterification by alcoholic hydrochloric acid yielded 

 a neutral ester, and this compound was isomeric with the former one. 

 The experiments of Leuchs (p. 18) have shown their exact nature, and 

 they are designated as the a- and /3-compounds. A similar isomerism 

 occurs with carbethoxyl diglycyl-glycine ester and with the correspond- 

 ing double amides. 



Polypeptides, which contain amino dicarboxylic acids or diamino 

 acids 'can also exist in isomeric forms; asparagyl-monoglycine can 

 exist in the two forms, 



CO NH.CH 2 .COOH COOH 



CH . NH 2 and CH . NH 2 



CH 2 . COOH CH 2 . CO N H . CH 2 . COOH 



as also the dipeptide of diaminopropionic acid : 



3* 



