Proteases as catalysts for enzymic syntheses of opioid peptides.
Two alternative pathways leading to protease-mediated syntheses of Leu- and Met-enkephalin are described. Each peptide bond of the opiate peptides was formed by either papain, or alpha-chymotrypsin catalysis. N alpha-t-Butyloxycarbonyl amino acids and peptides or their esters served as carboxyl components, whereas amino acid and peptide phenylhydrazides were used as acceptor nucleophiles. After removal of the protecting groups, the free pentapeptides were purified to homogeneity. They exhibited naloxone-reversible opiate like activity in guinea pig ileum and mouse vas deferens assays. The present study indicates that enzymic synthesis is a useful tool for rapid preparation of homogeneous peptides with highest obtainable optical purity.
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001681:Biological Assay; D002918:Chymotrypsin; D004723:Endorphins / Q000138:chemical synthesis*; D004743:Enkephalin, Leucine; D004744:Enkephalin, Methionine; D004745:Enkephalins / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D007202:Indicators and Reagents; D008297:Male; D008722:Methods; D051379:Mice; D010206:Papain; D014649:Vas Deferens / Q000187:drug effects
D000596:Amino Acids; D004723:Endorphins; D004745:Enkephalins; D007202:Indicators and Reagents; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D002918:Chymotrypsin; D010206:Papain