August 4, 1905.] 



SCIENCE. 



133 



ene and naphthalene in the tar, and an 

 analogous proposition may be true for the 

 proteins. Later, however, this important 

 generalization was reached ; it matters little 

 how the decomposition is effiected, the prod- 

 ucts of protein destruction are essentially 

 the same as long as brought about in the 

 presence of water, and all seem to be in the 

 nature of hydrolytic cleavages. The action 

 of boiling acid or alkali, steam under pres- 

 sure, pepsin and hydrochloric acid, trypsin 

 and weak alkalies, all lead to nearly the 

 same resultant products, and among these 

 certain a-amino acids are always the most 

 abundant. The conclusion follows, there- 

 fore, almost of necessity, that these are the 

 true nucleus groups and the question nat- 

 urally suggests itself, is it possible to put 

 these things together and build up any- 

 thing like a true protein. An answer to 

 the question has been slow in coming, but 

 a beginning has been made, and especially 

 through the experiments of Curtius and 

 Fischer. The condensation method fol- 

 lowed by the former is a general one, 

 through which a large number of amino 

 groups have already been combined. It 

 depends first on the production of hydra- 

 zides, then azides, which are very reactive, 

 and take on additional amino groups w4th 

 loss of hydronitric acid. For example, the 

 ethyl ester of hippuric acid condenses with 

 hydrazine hydrate to form the hydrazide : 

 CoH^CO . NHCHoCO . NH . NH,; 



this with nitrous acid gives the azide 



CeH^CO . NHCHXO . N3. 



By treatment with glycine under certain 

 conditions this reaction follows : 



CeH^CO . NHCHoCO . N3 + NH,CH,COOH = 



N3H + CeHsCO . NHCH,CO . NHCH.COOH. 



In other words, we have started with ben- 

 zoylglycine and have obtained benzoylgly- 

 cylglycine. This in turn may be used as a 

 new starting point, A silver salt is made. 



this turned into ester with ethyl bromide, 

 and then a new hydrazide and azide to be 

 combined with glycine, as before. These 

 steps will lead to benzoyl diglycylglycine, 

 and by using alanine, leucine or other 

 amino acid it will be seen that by repeat- 

 ing the processes extremely complex groups 

 may be finally built up. Curtius has car- 

 ried the reaction to the formation of ben- 

 zoyl hexaglycylglycine, 



C0H5CO. (NHCH,C0)eNHCH3C00H. 



Hippuryl and three alanine groups have 

 also been condensed to form benzoyl gly- 

 cyldialanylalanine. 



Fischer has worked from a different 

 standpoint. The study of various hydro- 

 lytic products from proteins, already re- 

 ferred to, and the isolation of certain other 

 groups by Fischer himself, led to the belief 

 that the complex molecules in the proteins 

 must be built up by the union of amino 

 acid groups. Various attempts had been 

 made to condense some of the simple amino 

 acids in anhydride form, but without much 

 success, until the first experiments were 

 made by Fischer in 1901. The starting 

 point of the series of condensations was 

 found in the product obtained from the 

 glycine anhydride described in 1888 by 

 Curtius and Goebel. This may be looked 

 upon as formed by the union of two mole- 

 cules of glycine with loss of two molecules 

 of water, and when digested with strong 

 hydrochloric acid suffers a peculiar decom- 

 position and yields a body to which Fischer 

 has given the name glycylglycine. 



CO :0H HHNCH, 



CO ■ CHj • NH 



I I 



NH • CH., • CO 



CH,NH:H HOIOC 



+ H2O = NH2CH2CONHCH2 • COOH 



Glycylglycine may be considered as the 

 first anhydride of glycine and is the char- 

 acteristic group in the hippuryl glycine 



