Opioid receptors (δ, μ and κ subtypes) belong to the G protein-coupled receptor (GPCR) superfamily. They are transmembrane proteins consisting of seven helices (TM1–TM7), connected by alternating extracellular and intracellular loops. They are responsible for pain perception being activated both by endogenous opioid peptides such as enkephalins or endorphins and by exogenous opiates, such as morphine.
The enkephalins ([Leu]enkephalin and [Met]enkephalin) are naturally occurring endogenous pentapeptides with the amino acid sequence Tyr-Gly-Gly-Phe-Leu/Met. Both enkephalins are potent agonists of the δ-opioid receptor, and to a lesser extent the μ-opioid receptor, with little to no effect on the κ-opioid receptor. Like most small peptides, the enkephalins are easily catabolised via enzymatic degradation and shows poor blood-brain barrier penetration. Attachment of sugars to peptides increases their penetration of the blood-brain barrier and affects the interactions with receptors.
In this study, the enkephalins containing the glucuronic acid conjugated onto the C-terminal residue have been investigated and their interaction with δ- and μ-opioid receptors has been analyzed in details to determine the probable receptor–ligand binding mode and to explain how the addition of the glucuronic acid influences on receptor–ligand interaction.
Acknowledgements: This work was supported by the Ministry of Science and Higher Education grant No 530-8372-D190-12.
