POLYPEPTIDES 39 



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

 glycine ester, 



C 4 H^ CHBr . CO NH . CH, . COCI + aNH,.CH, . COOC,H- HCI . NH, . CH, . COOC,H, 

 + C 4 H, . CHBr . CO NH . CH,. CO NH . CH, . COOC,H, 



which, on subsequent saponification and treatment with ammonia, gave 

 the tripeptide leucyl-glycyl-glycine, 



C 4 H, . CH(NHJ . CO NH . CH, . CO NH. CH, . COOH. 



The tetrapeptide leucyl-diglycyl-glycine, 



C 4 H, . CH(NHJ . CO NH . CH, . CO NH . CH, . CO NH . CH, . COOH, 

 was obtained when bromisocapronyl glycine was combined with glycyl- 

 glycine ester and treated in the same way. 



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 

 polypeptide ester, the synthesis of the complex octadecapeptide, com- 

 posed 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 chlor- 

 ide and combined with pentaglycyl-glycine. The resulting bromo 

 compound was treated with liquid ammonia and the decapeptide 1- 

 leucyl-octaglycyl-glycine, 



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

 was obtained. This gave the tetradecapeptide, leucyl-triglycyl-leucyl- 

 octaglycyl-glycine, 



C 4 H, . CH(NHJCO (NH . CH, . CO) S C 4 H, . CH(NH,) . CO (NH . CH, . CO), 



NH.CH, .COOH, 



on combination with bromisocapronyl diglycyl-glycyl chloride and 

 subsequent treatment with ammonia. 



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- 

 octaglycyl-glycine, 



C 4 H, . CH(NHJCO (NH . CH, . CO), C 4 H, . CH(NHJ . CO (NH . CH, . CO), 

 C 4 H, . CH(NHJ . CO (NH . CH. . CO), NH . CH, . COOH. 



