POLYPEPTIDES 29 



the alkyl groups attached to it, and that there is here another instance 

 of steric hindrance. 



The dipeptides of the oxy- and diamino acids have so far only been 

 prepared by this method by Fischer and Suzuki ; here, the methyl 

 esters of the amino acids were found to be most easily converted into 

 the anhydrides, and hydrolysis by alkali proceeded readily. 



Several of the dipeptides are most easily prepared in this way, and 

 they have been employed in the synthesis of more complex polypep- 

 tides. The method, however, does not lend itself to the preparation 

 of higher polypeptides, but it will be observed that pentaglycyl-glycine 

 and another compound, probably octaglycine anhydride, have been 

 prepared by heating the methyl ester of diglycyl-glycine. The various 

 compounds isolated by Curtius and his pupils, such as glycine an- 

 hydride and the biuret base, have been obtained from glycine ester. 



It must be noted that anhydrides are also formed when the dipep- 

 tides, prepared by the other methods, are heated to their melting-points, 

 e.g., leucyl-alanine anhydride from leucyl-alanine. 



Mixed anhydrides, as for example glycyl-alanine anhydride, can- 

 not be obtained by heating a mixture of the esters, since a complex 

 mixture would result, but they are easily prepared by the action of 

 ammonia upon the esters of the dipeptides obtained by the other 

 methods. The same anhydride is formed from the two corresponding 

 dipeptides as was first proved in the case of leucyl-glycine ester and 

 glycyl-leucine ester which gave leucyl-glycine anhydride : 



C 4 H 9 . CH . (NH,) . CO NH . CH, . COOC S H S = C 4 H 9 . CH CO NH 



| 

 NH C 



H,N . CH, . CO NH . CH(C 4 H 9 ) . COOC,H 8 = HN CH, CO 



lo CH(C 4 H,) NH 



These compounds, of which several have now been prepared, are of 

 great importance as they serve for the isolation of dipeptides from a 

 mixture of polypeptides and amino acids (see p. 81). On hydrolysis 

 they yield a mixture of the two dipeptides, which are composed of 

 the amino acids of which they are built up. Thus glycyl-1-tyrosine 

 anhydride yielded glycyl-1-tyrosine and 1-tyrosyl-glycine. The latter 

 compound is the first example of a polypeptide containing the tyrosine 

 radicle as the acyl group ; in all the other polypeptides in which 

 tyrosine is present it stands at the end of the chain. 



The compounds which have been obtained can be seen from the 

 accompanying list 



I + C,H 8 OH 



:o CH, 



+ C,H 8 OH 

 Cf 



