Opioid deltorphin C analogues containing cis- or trans-2- or 3- or 4-aminocyclohexanecarboxylic acid residues

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) anal ogues containing cis- and trans- 2 or 3- or 4- aminocyclohexanecarboxylic a cid (ACCA) residues at position 3. ACCA-peptides showed high resistance to degradation by plasma or blain enzymes, negligible affinity for the kappa-b inding site and modest delta- and/or mu-receptor affinities. Both [cis-3-AC CA(2)]Del-C analogues and one trans isomer are the only deltorphin analogue s of this series exhibiting an appreciable delta-affinity and selectivity. These data suggest that the presence of st conformationally constrained ACC A residue in position 2 of the "message" sequence of deltorphin C is slight ly tolerated.