22 THE CHEMICAL CONSTITUTION OF THE PROTEINS 



The Polypeptides. 



Our knowledge of the structure of the protein molecule has been 

 given us by the systematic researches of Emil Fischer and his pupils 

 which were commenced in 1901, the combinations together of the amino 

 acids being termed the polypeptides. This designation is in imitation 

 of that of the carbohydrates, where we differentiate between mono-, di-, 

 tri-, poly-saccharides, and it retains the word peptone, on account of 

 the very similar properties of these substances to peptone, which most 

 probably consists of a mixture of polypeptides. 



Three general methods have been devised for the synthesis of the 

 polypeptides which are best described separately. 



Method I. Synthesis from the Esters. 



The ester of glycine was first prepared, as previously mentioned, by 

 Curtius in 1883, and it was observed by Curtius and Goebel, in 1888, 

 that the ester lost alcohol and was converted into 2, 5-diketo- or diaci- 

 piperazine. 



Similar compounds leucinimide and lactimide had been obtained 

 from leucine and alanine. These anhydrides form the starting-point in 

 the synthesis of the polypeptides by this method, and they are best ob- 

 tained by heating the ester of the amino acids in a sealed tube to 

 150-180 C. for some hours. 



Fischer and Fourneau, in 1901, found that 2, 5-diketopiperazine, or 



glycine anhydride, as it is now best termed, was converted by boiling 



with concentrated hydrochloric acid into the hydrochloride of an amino 



acid of the formula C 4 H 8 N 2 O 3 , from which they obtained the free acid 



by treatment with the calculated quantity of caustic soda, or by means 



of silver oxide. Its formation is represented by the equation 



NH CH a CO 



CO 



The compound is the first anhydride of glycine, and was termed 

 glycyl-glycine, the group NH 2 . CH 2 . CO being called the glycyl group. 



By treating glycine anhydride with alcoholic hydrochloric acid, 

 glycyl-glycine ester resulted : 



NH CH 2 CO 



I I + C 2 H 6 OH = NH 2 . CH 2 . CO NH . CH 2 . COOC 2 H 5 . 



CO CH a NH 



Both the free acid and its ester have a great tendency to become recon- 

 verted into glycine anhydride, and both compounds are characterised by 



| | + H 2 O = NH 2 . CH 9 .CO NH.CH 2 .COOH. 



i CH NH 



