SYNTHESIS OF PROTEINS 13 



If the bromisocapronylglycylchloride be made to act upon glycyl- 

 glycin ester, and the product be treated in the same way, the 

 tetrapeptid, leucyl-diglycyl glycin results: 



C4H9.CH(NH2).CO.NH.CH2CO.NH.CH2CO.NH.CH2.COOH. 



These methods of synthesis proved inadequate where hydroxy- 

 amino-acids are concerned, because the phosphorus penta- 

 chloride, used in the formation of the acid chloride, attacks the 

 OH group. It was, however, ascertained that the OH could be 

 protected by acting upon the hydroxy amino-acid with methyl 

 ehlorcarbonate (20), which converts the OH into — OCO2CH3, 

 which is not attacked by PCI5 and is readily removed by hy- 

 drolysis. In this way it has proved possible to introduce phenyl- 

 carboxylic acids, such as tyrosin, into poly-amino-acid chains. 



By these methods, and modifications of these methods, Fischer 

 has succeeded in building up long chains of amino-acid groups, 

 these chains being collectively termed, by Fischer, peptids. 

 Chains consisting of two links, i.e., combinations of two amino- 

 acids, Fischer terms dipeptids; such, for example, are glycyl- 

 glycin, alanyl-alanin and leucyl-leucin ; chains consisting of three 

 links he terms tripeptids, such being, for example, diglycyl- 

 glycin, and leucyl-glycyl-glycin; chains consisting of four links 

 are termed tetrapeptids, and so on, the higher members of the 

 series being coUectivelj^ termed polypeptids. 



The surpassing interest of these investigations lies in the fact 

 that Fischer considers many of his polypeptids to be, in all proba- 

 bility, identical with some of the natural peptones and sub- 

 peptones; while others probably merit inclusion among the 

 proteins themselves. Thus the octadecapeptid 1-leucyl-triglycyl- 

 1-leucyl-triglycyl-l-leucyl-octaglycyl-glycin, and the tetradeca- 

 peptid 1-leucyl-triglycyl-l-leucyl-octaglycyl-glycin so closely re- 

 semble, in general properties, the ordinary proteins, that, as 

 Fischer puts it, they would have been classed as proteins had 

 they been first met with in natm-e (18) (19). Thus they give 

 the biuret reaction, form opalescent watery solutions, and the 

 tetradecapeptid is precipitated bj^ ammonium sulphate, by tannic 

 acid and by phosphotungstic acid. As they do not contain 

 tyrosin, tryptophane or cystin they fail to give such protein 

 color reactions as depend upon the presence of these groups. 

 The molecular weight of the octadecapeptid is 1213, and the 



