POLYPEPTIDES. 89 



(brompropionyl glycine). On subsequent treatment with ammonia the halogen 

 (Br) is replaced by NH 2 and the dipeptide alanylglycine 



CH 3 CHNH 2 CO.NHCH 2 COOH+NH4Br 



is obtained. By the second action of brompropionylchloride and then treatment 

 with NH 3 we introduce a new alanyl group and the tripeptide alanyl-alanyl 

 glycine is prepared. By the action of a halogen derivative of an acid radical 

 another amino-acid residue can be introduced, and the chain of amino groups 

 can be thus extended. 



I The prolongation of the chain on the other side, namely, at the carboxyl, 

 FISCHER has accomplished by chlorination of the amino-acids by special treatment 

 with phosphorus pentachloride. The carboxyl is thus transformed into COO, 

 while the acid at the same time fixes a molecule of HC1, for example CHaCHNH^Ci 



COC1 



Just as in the case of the carboxyl group of an amino-acid, so also can a poly- 

 peptide or its halogen acyl combination be chlorinated and then combined with 

 a new amino-acid, or a new peptide. As an example, FISCHER, from a-brom- 

 isocapronyldiglycyl glycine, first prepared a-bromisocapronyldiglycylglycyl chlo- 

 ride, and then with diglycylglycine he obtained the heptapeptide leucyl- 

 pentaglycylglycine, 



C 4 H 9 CH(NH 2 )CO.(NHCH 2 CO) 6 .NHCH 2 COOH. 



For the various combinations of the optically active amino-acids to poly- 

 peptides it was important to possess methods of preparation of these amino-acids, 

 and for this purpose FISCHER in many cases used the so-called WALDEN'S reversion. 

 This consists in that one optically active amino-acid, for example the Z-form, is 

 transformed into the corresponding halogen fatty acid by the action of nitrosyl 

 bromide, yielding the optical antipode the d-form. By the action of ammonia 

 the d-amino-acid is now obtained which in the above-mentioned manner can be 

 retransformed into the /-form. Thus from d-leucine we first obtain Z-bromiso- 

 caproic acid and then by the action of ammonia /-leucine and in the preparation 

 of the polypeptides the same occurs. Thus, for example, if by reversion d-leucine 

 is changed first into Z-bromisocapronyl chloride, if this last is combined with 

 Meucine, then we obtain the dipeptide Z-leucyl-/-leucine. On combination with 

 diglycylglycine the tetrapeptide /-leucyl-diglycyl glycine is produced. WALDEN'S 

 reversion does not take place with all amino-acids; other methods can also be 

 used to obtain the optical antipodes, such as the preparation of the alkaloidal 

 salts of the benzoyl or formyl combinations of the racemic amino-acids. 



The /3-naphthalinsulpho combination of the polypeptides and peptones may 

 serve, as FISCHER, ABDERHALDEN and FUNK * have shown, in explaining the 

 structure of these bodies. By the action of /3-naphthaline sulphochloride the 

 NH 2 groups existing at the beginning of the chain in the amino-acids react there- 

 with and on subsequent total hydrolysis this naphthaline-sulpho combination 

 remains unsplit. Thus for instance we can differentiate between glycylalanine 

 and alanylglycine because after hydrolysis in the first case we obtain naphthalin- 

 sulphoglycine and alanine and in the second naphthalin-sulphoalanine and 

 glycocoll (glycine). Tyrosine may, depending upon whether the NH 2 as well 

 as the OH groups are free or not or if only one is available, yield di- or mononaph- 

 thalinsulpho-derivatives and in this way we can also draw conclusions as to the 

 structure of tyrosine containing peptides. 



The previously mentioned deamidation method of van Slyke (page 78) where 

 oxyacids are formed by the action of HNO 2 upon the NH 2 groups can also give 



1 E. Fischer and Abderhalden, Ber. d. d. Chem. Gesellsch., 40; Abderhalden and 

 C. Funk, Zeitschr. f. physiol. Chem., 64. 



