THE SYNTHESIS OF THE PROTEINS 31 



combined with glycine ester, when it yielded bromisocapronyl-glycyl- 

 glycine ester, 



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

 HC1 . NH 2 . CH 2 . COOC 2 H 5 +"C 4 H 9 . CHBr . CO NH . CH 2 . CO 

 NH.CH 2 .COOC 2 H 5 



which on subsequent saponification and treatment with ammonia, gave 

 the tripeptide leucyl-glycyl-glycine, 



C 4 H 9 . CH(NH 2 ) . CO NH . CH 2 . CO NH . CH 2 . COOH. 



If combined with glycyl-glycine ester and treated in the same way 

 the tetrapeptide leucyl-diglycyl-glycine, 



C 4 H 9 . CH(NH 2 ) . CO NH . CH 2 . CO NH . CH 2 . CO NH . CH 2 . COOH, 



was obtained. 



Not only was it possible to prepare the acid chloride of a halogen 

 acyl derivative of an amino acid, but also that of a di-, tri-, etc., peptide 

 by exactly the same means. Thus, the compound bromisocapronyl- 

 diglycyl-glycyl chloride can be obtained, and by condensing it with the 

 esters of amino acids and of polypeptides Fischer has prepared a hexa-, 

 a hepta-, and a deca- peptide (see tabulation). 



These compounds already exhibit the extraordinary possibilities of 

 synthesis by this method. By continuing the process of preparing the 

 acid chloride of a new polypeptide and again combining it with a poly- 

 peptide ester, the synthesis of the complex octadecapeptide, composed 

 of fifteen glycine residues and three leucine residues, was effected in 

 1907. Its preparation is the best illustration of how this method lends 

 itself to the synthesis of the polypeptides. 



Bromisocapronyl diglycyl-glycine was converted into its acid chloride 

 and combined .with pentaglycyl-glycine. The resulting bromo com- 

 pound was treated with liquid ammonia and the decapeptide 1-leucyl- 

 octaglycy 1 -glycine, 



C 4 H 9 . CH(NH 2 ) . CO (NH . CH 2 . CO) 8 NH . CH 2 . COOH, 



was obtained. This gave, on combination with bromisocapronyl 

 diglycyl-glycyl chloride and subsequent treatment with ammonia, the 

 tetradecapeptide, leucyl-triglycyl-leucyl-octaglycyl-glycine, 



C 4 H 9 . CH(NH 2 )CO (NH . CH 2 . CO), C 4 H 9 . CH(NH 2 ) . CO (NH . CH 2 . CO) 8 



NH.CH 2 .COOH. 



A repetition of the process of combining this new compound with 

 bromisocapronyl-diglycyl-glycyl chloride and treating with ammonia 

 yielded the octadecapeptide, leucyl-triglycyl-leucyl-triglycyl-leucyl-octa- 

 glycyl-glycine, 



C 4 H 9 . CH(NH 2 )CO (NH . CH 2 . CO) 3 C 4 H 9 . CH(NH 2 ) . CO (NH . CH 2 . CO) 3 

 C 4 H 9 . CH(NH 2 ) . CO (NH . CH 2 . CO) 8 NH . CH 2 . COOH. 



