THE SYNTHESIS OF PROTEINS . 141 



By saponification of this ester, free chloracetyl-glycyl-glycine is 

 obtained. On now treating this with a concentrated aqueous solution 

 of ammonia, the chlorine atom in the chloracetyl group becomes, by 

 a usual reaction, replaced by an amino-group, and thus Diglycyl-glycine 

 is obtained: 



C1CH 2 .CO.NH.CH 2 .CONH,CH2COOC 2 H 5 + 2NH 3 = 

 (Chloracetyl glycyl-glycine ester) 



H 2 N.CH 2 .CONH.CH 2 CONH.CH 2 COOC 2 H 5 + NEUC1 



(Diglycyl-glycine ester). 



In other words, the chloracetyl-group, introduced to protect the 



NH 2 -group of the amino-acid is, after it has performed its protective 

 function, itself transformed into an amino-acid-group, through the 

 replacement of the halogen atom by NH 2 . Obviously, other halogen- 

 containing acid groups may be used in place of chloracetyl, and in this 

 way a great variety of amino-acid-groups can be introduced into the 



NH2-group. Among others the following are employed: 

 Chloracetyl chloride for the introduction of glycyl. 

 a-Bromopropionyl chloride for the introduction of alanyl. 

 a-Bromisocapronyl chloride for the introduction of leucyl. 

 a-Phenylbromopropionyl chloride for the introduction of phenyl- 



alanyl. 



a-S-Dibromovaleryl chloride for the introduction of prolyl. 



By this method the chain of amino-acids is lengthened at the amino- 

 group end. Theoretically it appeared possible to also lengthen the 

 chain at the carboxyl-end of the molecule, by acting upon the esters 

 of the amino-acids with the acid chlorides of other amino-acids. Until 

 1904, however, the acid chlorides of amino-acids were unknown, and 

 all attempts to prepare them had failed, owing to the same reason 

 which limits the use of the first method of synthesizing poly-amino- 

 acids described above, namely the reactivity of the NH 2 -group. It 

 will be recollected that Fischer found that the NH 2 -group could be 

 protected by the introduction of radicals, and, utilizing this fact, in 

 1904 he succeeded in devising a method of preparing the acid chlorides 

 of the amino-acids. The acid chlorides thus prepared, react with the 

 esters of other amino- or polyamino-acids to form polyamino-acid 

 chains of greater length. Thus: 



C4H 9 CHBr.CO.NH.CH 2 .COCl + 2NH 2 .CH 2 .COOC 2 H 5 = 



(Bromisocapronyl-glycyl chloride) Glycine ester) 



+ C4H9CHBrCONH.CH 2 CO.NH.CH 2 COOC2H 5 

 (Glycine ester hydrochloride) (Bromisocapronyl-glycyl-glycine ester) 



Subsequent saponification of the bromisocapronyl-glycyl-glycine 

 ester and treatment with ammonia yields the polyamino-acid or 

 (tripeptide) , Leucyl-glycyl-glycine : 



aH 9 CH(NH 2 )CO.NH.CH 2 CONH.CH2.COOH 



