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

MARASTONI M.;GUERRINI R.;BALBONI, GIANFRANCO;SALVADORI S.;FANTIN G.;FOGAGNOLO M.;LAZARUS L.H.;TOMATIS R.

1999-01-01

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Abstract

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.