Enzymatic synthesis of Leu- and Met-enkephalin

The protease-catalyzed synthesis of Leu- and Met-enkephalin is reported. Each peptide bond of the endogeneous opiate-pentapeptides was formed either by papain or α-chymotrypsin catalysis. N-acyl amino acids and peptides or their ester derivatives served as substrates whereas amino acid and peptide phenylhydrazides were used as nucleophiles. The free pentapeptides exhibited naloxone-reversible opiate-like activity in guinea-pig ileum and mouse vas deferens assays. The present study suggests the usefulness of enzymic peptide synthesis which allows rapid preparation of homogeneous compounds with high optical purity.