180 LECTURE IX. 



In the same manner, although with more difficulty, alanine hydride 

 gives us alanyl-alanine; while from leucinimide we get leucyl-leucine. 



A second method of coupling the amino acids consists in uniting them 

 with an acid radical containing halogen, and then replacing the halogen 

 by an NH2 group. The following may act as an example of this form of 

 polypeptide synthesis: 



In order, for instance, to produce glycyl-glycine, glycocoll is caused to 

 unite with chloroacetyl chloride. Chloroacetyl-glycine results: 



Cl . CH 2 . CO . C1 + NH 2 . CH 2 . COOH = Cl . CH 2 . CO . NH . CH 2 COOH 



""" + HC1. 



Chloroacetyl Glycocoll Chloroacetyl-glycine 



chloride 



If ammonia is allowed to act on chloroacetyl-glycine, we immediately 

 obtain glycyl-glycine: 



C1CH 2 . CO . NH . CH 2 COOH + 2 NH 3 = NH 4 C1 + 



Chloroacetyl-glycine 



NH 2 . CH 2 . CO . NH . CH 2 COOH. 



Glycyl-glycine 



We can then take this dipeptide, glycyl-glycine, treat it again with 

 chloroacetyl chloride, thus adding another glycyl radical to it. Treating 

 the substance thus formed with ammonia gives us digly cyl-glycine : 



NH 2 . CH 2 . CO . NH . CH 2 . CO . NH . CH 2 . COOH. 



Naturally, by following out this same method, we can use other acid 

 radicals, thus introducing other amino acids. Should we, for instance, 

 desire to produce alanyl-glycine, we start with glycocoll and bromo- 

 propionyl chloride, forming a-brom-iso-capronyl chloride, which corre- 

 sponds to leucine. 



It will be noticed that, by following the above method, it is only possible 

 to extend the chain in one direction, towards the amine group. It 

 was, of course, also desirable to add new amino acids to the carboxy side. 

 This was accomplished by chlorinating the amino acids. If phosphorus 

 pentachloride be added to an amino acid under definite conditions, the 

 carboxyl group is changed into the COC1 group. The free amino acid also 

 combines at the same time with a molecule of hydrochloric acid. The 

 hydrochloride of the ammo-acid-chloride results: 



R . CH . COC1 



NHc 



[ 2 . HC1. 



The peptides can, naturally, be chlorinated, and the grouping further 

 extended. By this means we quickly obtain long chains. 



