title: Minimum structure opioids-dipeptide and tripeptide analogs of the enkephalins.
abstract: Through a systematic reduction of peptide structure, a series of 25 tripeptide and 5 dipeptide amide and alcohol analogs of enkephalin were synthesized and assayed in vitro on the stimulated guinea pig ileum. Tyr-Pro-Phe-NH2, Tyr-D-Ala-Phe-NH2, Tyr-D-Ala-Phe-ol and Tyr-D-Phe-Phe-NH2 had 20-25% the potency of Met-enkephalin. Four aromatic alkylamides of the dipeptide Tyr-D-Ala were made with benzylamine, phenethylamine, phenylpropylamine and phenylbutylamine. All had full naloxone reversible enkephalin-like activity in the ileum assay. Tyr-D-Ala-phenylpropylamide has about 80% the potency of Met-enkephalin in vitro, and is equipotent with Tyr-D-Ala-Gly-Phe-Met-NH2 in producing analgesia in mice after intraventricular administration. Tyr-D-Phe-NH2 is the smallest peptide to show full intrinsic enkephalin-like activity in vitro, although its potency is very low.
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004151:Dipeptides; D004723:Endorphins / Q000138:chemical synthesis*; D004745:Enkephalins / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009842:Oligopeptides; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D004151:Dipeptides; D004723:Endorphins; D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid