Synthesis of peptides of methionine and their cleavage by proteolytic enzymes.

In a previous communication from this laboratory (l), a method was described for the enzymatic resolution of Dr.,-methionine. The ready availability of the optically active enantiomorphs has made possible the application of the carbobenzoxy method to the synthesis of peptides of Land n-methionine. A search of the literature has indicated that the only methionine peptide described thus far is glycyl-L-methionine (2), which was obtained by the treatment of L-methionine with chloroacetyl chloride, followed by the amination of the resulting chloroacetylamino acid. The rotation of the peptide was not reported, however, and, as is noted in the experimental section of this communication, the melting point of this product is about 55’ lower than that found for glycyl-nmethionine prepared by the carbobenzoxy method. In what follows, there is described the synthesis of a series of methionine peptides and peptide derivatives, and a number of these have been examined with regard to their susceptibility to the hydrolytic action of several proteolytic enzymes. In addition, the availability of such peptides of methionine makes possible the study of other metabolic reactions involving compounds in which this amino acid is bound in peptide linkage. The results of such studies will be reported in future communications. Synth,esis of Peptides of Methionine-In the experimental section, directions are given for the synthesis of the free peptides glycyl-nand n-methionine, Land n-methionylglycine, ru-L-glutamyl-L-methionine, L-