THE CHEMISTRY OF THE PROTEINS 109 



and chloracetylglycylglycinester gives diglycylglycinester, from 

 which on hydrolysis the free acid is obtained. 



In just the same way the alanyl and leucyl radicles can be 

 introduced by using a-brompropionylbromide and a-bromiso- 

 capronylchloride. Leucylproline can be obtained in this manner, 

 the a-pyrrolidine carboxylic acid also lending itself to synthesis 

 by this reaction. The residue — prolyl — can be introduced by 

 combining amino acids with the chloride of a-8-dibromvalerianic 

 acid ; the compound obtained on treatment with ammonia, just 

 as in the synthesis of a-pyrrolidine carboxylic acid, after 

 exchanging the Br atoms for NH 2 , loses ammonia, forming the 

 prolyl dipeptide, e.g. prolylalanine. Not only can the simple 

 monoamino acids be combined by this method, but also cystine, 

 from which, e.g., dialanylcystine results. The aspartic acid 

 radicle is introduced by means of fumarylchloride ; when 

 combined with alanine, fumaryldialanine is formed ; this adds 

 on ammonia, yielding asparagyldialanine. Lastly, the phenyl- 

 alanine residue can be attached by means of phenylbrom- 

 propionyl chloride. 



A large number of mixed dipeptides, and also of tri-, tetra-, 

 etc., peptides, have been prepared by this method, which, how- 

 ever, only admits of the lengthening of the chain in one direction 

 — namely, on the side of the amino group. 



It was of extreme importance to be able to lengthen the 

 chain upon the side of the carboxyl group, and this is possible 

 only by means of the acid chloride. As previously stated, the 

 acid chlorides of the amino acids and polypeptides were not 

 known, but that the acid chloride of the carbethoxy derivative 

 was prepared by the action of thionylchloride upon it. The 

 presence of the halogenacyl radicle in the amino acid, such 

 as bromcapronyl, again allows of the formation of the acid 

 chloride of the amino acid or polypeptide, and this compound 

 reacts with the esters of other amino acids in the following way : 



C 4 H 9 . CHBr . CO . NH . CH 2 . COC1 + 2NH, . CH v COOC 2 H 5 

 = HC1. NH,.CH 2 .COOaH 5 " + 

 C 4 H 9 .CHBr . CO. NH. CH., .CO. NH . CH 2 :COOC,H 5 



Subsequent hydrolysis of the ester and treatment with 

 ammonia gives the polypeptide. This process can be carried 

 out indefinitely by again making the acid chloride of the new 

 compound and condensing it with an amino acid or a poly- 

 peptide. Any conceivable combination can be prepared by 



