46 THE CHEMICAL CONSTITUTION OF THE PROTEINS 



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 precautions. The question of their structure 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, . CO NH . CH, . COOH NH, . CH, . C(OH)=N . CH, . COOH 



NH 8 . CH, . CO NH . CH, . COO NH, . CH, . C(OH)=N . CH, . 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, thus leucyl-diglycyl-glycine in its amorphous 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. 



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.CHj.COOH COOH 



CH . NH, and CH . NH, 



CH,.COOH CH,.CO NH.CHj.COOH 



as also the dipeptide of diaminopropionic acid : 



NH, . CH, . CH(NHJ . CO NH . CH, . CH(NHJ . COOH 

 NH, . CH, . CH(NHJ . CO NH . CH . COOH 



CH,.NH, 



The diketopiperazines which are so closely related to the dipeptides 

 can also occur in a keto- or -enol form ; the possibilities are : 



/-^ .-, V -, V 



NH/ >NH Nf \N Nf >NH 



\CHg- CCK \CHr-C(OH)^ \ CH, CO/ 



The existence of the -enol form was emphasised by the fact that in 

 the hydrolysis of alanine anhydride by alkali, a transient formation of 

 an alkali compound was observed. 



