Endogenous peptides for delta opioid receptors and analogues

The discovery of the endogenous opioid peptides leucine-enkephalin (H-TyrGly-Gly-Phe-Leu-OH) and methionine-enkephalin (H-Tyr-Gly-Gly-PheMet-OH) [1] (Fig. 1) and the suggestion, first from pharmacological studies [2,3] and later from molecular cloning [4-7], that there are three opioid receptors (mu, delta, and kappa) have had an enormous impact on the search for better opioid analgesics that would not possess the severe toxicities and other undesirable biological activities of the alkaloid morphine and related compounds. The delta opioid receptor, and selective ligands for this receptor that also haveminimal side effects, have been amajor target in opioid research ever since.