TRE 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-6-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,, loses ammonia, forming the 
prolyl dipeptide, ¢.g. prolylalanine. Not only can the simple 
monoamino acids be combined by this method, but also cystine, 
from which, e.g., dialanyleystine 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,H,. CHBr. CO. NH.CH,. COCI + 2NH,. CH,.COOC,H, 
= HCl. NH,. CH;. COOC,H, + 
C,H,.CHBr.CO.NH:CH,.CO NH .CH,. COOC,H, 
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 
