[Leu5]-Enkephalin, naturally present in mammalian brain, is one of the endogenous pentapeptides with morphine-like properties. [Leu5]-Enkephalin exhibits agonistic actions at both the δ- and μ-opioid receptors, with substantially greater preference for the former, but shows little effect on the κ-opioid receptor. In humans, the δ-opioid receptor is most heavily expressed in basal ganglia and neocortical regions, and associated with pain, depression, as well as learning and memory. [Leu5]-Enkephalin, along with the other endogenous pentapeptide, [Met5]-enkephalin, have been found to behave as potent, yet short-lived opiates in vivo.

References:

1. Sengul G, Watson C. Chapter 6 - Spinal Cord: Regional Anatomy, Cytoarchitecture and Chemoarchitecture. The Human Nervous System (Third Edition), 2012.

2. Peppin JF, Raffa RB. Delta opioid agonists: a concise update on potential therapeutic applications. Journal of Clinical Pharmacy and Therapeutics, 2015, 40(2): 155-166.

3. Meunier JC, Moisand C. Binding of Leu5-enkephalin and Met5-enkephalin to a particulate fraction from rat cerebrum. FEBS Letters, 1977, 77(2): 209-213.

4. DiMaio J, Nguyen TM, Lemieux C, et al. Synthesis and pharmacological characterization in vitro of cyclic enkephalin analogues: effect of conformational constraints on opiate receptor selectivity. Journal of Medicinal Chemistry, 1982, 25(12): 1432-1438.