Conformationally constrained deltorphin analogs with 2-aminotetralin-2-carboxylic acid in position 3.

Two approaches to the design of very active and highly selective delta opioid peptides were used to obtain new deltorpin analogs with altered hydrophobic and stereoelectronic properties. Deltorphin I and II analogs were synthesized involving the substitution of Ile instead of Val at positions 5 and 6 in the address domain and 2-aminotetralin-2-carboxylic acid (Atc) instead of Phe in the message domain. The peptides were agonists in the subnanomolar range in the MVD assay and in the micromolar or higher range in the GPI assay, showing a very high selectivity for delta receptors.