THE PROTEINS 87 



This theory of the constitution of proteins was based on the fact that a 

 similar grouping was known to occur in leucinimide, obtained by the con- 

 densation of two molecules of leucine ; 



C 4 H 9 



NH CO 



I I 



CO NH 



I 

 C 4 H 9 



and also by the fact that only a small proportion of the NH 2 groups present 

 in the separated amino-acids exist free in the protein molecule. By the 

 action of nitrous acid the terminal NH 2 groups are split off and replaced by 

 OH. When proteins are treated with nitrous acid only a small proportion of 

 the total nitrogen is split off in this way. The linking of the amino groups 

 must therefore take place by means of the nitrogen, i.e. by NH groups. 

 Synthetic experiments have fully confirmed this hypothesis. In 1883 

 Curtius obtained a substance giving the biuret reaction, the so-called 

 ' biuret base,' by the spontaneous polymerisation of glycocoll ester. This 

 base has been shown by recent researches to consist of four glycine molecules 

 arranged together in an open chain. The clue to the structure of this base 

 was given by Fischer, who has devised a number of ingenious methods for 

 combining together amino-acids of any character and in any number. Thus 

 from two molecules of glycine we may obtain the compound glycyl glycine, 

 as follows : 



NH 2 .CH 2 .COOH + HNH.CH 2 .COOH - H 2 = 

 NH 2 .CH 2 .CO.NH.CH 2 .COOH 



This may be prepared in various ways. In one method glycine is converted into 

 its ester CH 2 .NH 2 .CO.OCH 3 . In a watery solution this undergoes spontaneous con- 

 version into glycine anhydride which belongs to the class of bodies known as diketo- 

 piperazins, as follows : 



CH 2 CO 

 2NH 2 .CH 2 CO.OCH 3 - 2CH 3 OH + NH<^ 



methyl alcohol NCO CH 



On treating this with dilute alkali it takes up water, splitting in the situation of the 

 dotted line and forming glycyl glycine, NH 2 CH 2 CO.NH.CH 2 COOH. 



More general methods have been devised by Fischer for the same purpose, depending 

 on the use of the halogen acyl chlorides. 



Thus chloracetylchloride and alanine yield chloracetalanine : 



C1.CH 2 .COC1 + NH 2 .CH(CH 3 ).COOH = 

 C1.CH 2 .CO - NH.CH(CH 3 )COOH + HC1. 



By the subsequent action of ammonia, the halogen group is replaced by the amino 

 group, and a dipeptide results : 



