SYNTHESIS AND OPIOID ACTIVITY PROFILES OF PROENKEPHALIN (100-111) ANALOGS

Twelve analogs of the peptide Tyr-Gly-Gly-Phe-Met-Lys-Arg-Tyr-Gly-Gly- Phe-Met-OH (BI), which corresponds to the peptide segment encompassing residues 100-111 of proenkephalin, were synthesized by the solid-phas e method. The performed structural modifications included omission of the Lys or Arg residue, substitution of Lys by Arg, Arg by Lys, Gly by D-Ala and Met by Leu, and amidation of the C-terminal carboxylic grou p. Opioid activities of the peptides were determined in the guinea pig ileum (GPI) assay and in the mouse vas deferens (MVD) assay. Some ana logs showed higher agonist potency than Leu-enkephalin in the GPI assa y, whereas all compounds were less potent than Leu-enkephalin in the M VD assay.