Synthesis of peptides of L-serine and their cleavage by proteolytic enzymes.

An earlier communication (1) dealt with the application of the carbobencoxy method to the synthesis of peptides of L-serine. This work has now been extended, and an examination has been made of the response of several serine peptides and peptide derivatives to the action of peptidases. Synthesis of New Serine Peptides-In the course of the present study, the following new peptides were made: glycyl-L-serine, L-alanyl-L-serine, L-serylglycyl-L-glutamic acid, L-seryl-L-alanyl-L-glutamic acid, and L-serylglycyl-L-serine. In addition, several derivatives of these peptides are described in the experimental section of this communication. For the preparation of these compounds, the methods used previously (1) in the synthesis of L-serylglycine, L-seryl-L-alanine, and L-seryl-L-serine were modified only slightly. It was noted earlier (1) that the synthesis of seryl peptides by means of the reaction of carbobenzoxy-L-serinazide with the ester of an amino acid (or peptide) may be attended by the formation of 4-carbobenzoxyaminooxazolidone-2 as a by-product, thus reducing appreciably the yield of the desired peptide ester. In order to diminish the extent of this side reaction, the syntheses involving the use of the azide were conducted in a cold room at 4”. In the saponification of the carbobenzoxypeptide esters to the corresponding carbobenzoxypeptides, the yields were frequently unsatisfactory when the reaction was conducted in the usual manner; i.e., the treatment of the ester with 1.1 equivalents of alkali in methanol (or acetone) at room temperature for about 20 minutes, followed by acidification of the reaction mixture. With several of the serine-containing carbobenzoxypeptide esters, it was found by means of paper chromatography that the acidified filtrate, after removal of the expected carbobenzoxypeptide, contained appreciable quantities of ninhydrin-reactive substances. This suggests that