3-aminocyclohexanecarboxylic-acid and 2-aminocyclohexanecarboxylic-acid

The solid phase synthesis, based on the Fmoc chemical protocol, was used to prepare ten deltorphin C (Del-C; H-Tyr-D-Ala-Phe-Asp-Val-Val-Gly-NH2) analogues containing cis- and trans- 2 or 3- or 4- aminocyclohexanecarboxylic acid (ACCA) residues at position 2. ACCA-peptides showed high resistance to degradation by plasma or brain enzymes, negligible affinity for the kappa-binding site and modest delta- and/or mu-receptor affinities. Both [cis-3-ACCA2]Del-C analogues and one trans isomer are the only deltorphin analogues of this series exhibiting an appreciable delta-affinity and selectivity. These data suggest that the presence of a conformationally constrained ACCA residue in position 2 of the "message" sequence of deltorphin C is slightly tolerated.

Topics: Amino Acids; Amino Acids, Cyclic; Analgesics, Opioid; Animals; Brain; Cyclohexanecarboxylic Acids; Cyclohexylamines; Guinea Pigs; Ileum; In Vitro Techniques; Male; Mice; Molecular Conformation; Oligopeptides; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Spectrophotometry, Ultraviolet; Stereoisomerism; Vas Deferens