OPIOID INFIDELITY - NOVEL OPIOID-PEPTIDES WITH DUAL HIGH-AFFINITY FORDELTA-RECEPTOR AND MU-RECEPTOR

Deltorphins represent the paragon of delta-opioid-receptor ligands of natural origin, since they exceed the affinity and selectivity of the endogenous enkephalins by orders of magnitude. A series of opioid pept ides have been developed in which the change in a single amino acid ca uses an extraordinary increase in mu-receptor binding while maintainin g high affinity for the delta-receptor. The peptides appear to have a similar extended conformation in solution with a type-1 p-turn in the N-terminus region, suggesting that tertiary architecture plays a pivot al role in enabling the peptide to bind indiscriminately to mu- and de lta-receptors. These dual-affinity peptide ligands can serve to mask d elta- and mu-receptors while mapping kappa-receptors in the nervous sy stem, to provide an understanding of the differences and similarities in the structure of the binding domains of delta- and mu-receptors, an d might lead to a comprehensive new regime for the clinical management of acute and chronic pain.