Leucine-Enkephalin
Leucine-enkephalin is an endogenous pentapeptide neurotransmitter that binds mu and delta opioid receptors to produce analgesic, anxiolytic, and reward-related effects in the central nervous system.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C28H37N5O7 |
| Molecular Weight | 555.62 g/mol |
| CAS Number | 58822-25-6 |
| IUPAC Name | Tyr-Gly-Gly-Phe-Leu |
| Peptide Class | Pentapeptide |
| Amino Acid Composition | Tyr-Gly-Gly-Phe-Leu |
Structure
Leucine-enkephalin (Leu-enkephalin) is a pentapeptide with the sequence Tyr-Gly-Gly-Phe-Leu. It belongs to the enkephalin family, which shares a conserved N-terminal Tyr-Gly-Gly-Phe motif differing only at the fifth residue (Leu-enkephalin vs. Met-enkephalin). The tyrosine residue is critical for opioid receptor interaction, mimicking the N-terminal phenol of morphine.
The flexible glycine-glycine spacer allows the peptide to adopt conformations suitable for receptor binding, while the hydrophobic C-terminal residue (leucine) contributes to selectivity profile differences between the two enkephalins.
Opioid Receptor Binding
Leu-enkephalin binds both mu-opioid receptors (MOR) and delta-opioid receptors (DOR), with moderate selectivity for DOR over MOR. Both receptors are G protein-coupled receptors that inhibit adenylyl cyclase, reduce cAMP levels, and activate inwardly rectifying potassium channels when stimulated.
Endogenous enkephalin signaling produces analgesia, particularly in spinal and supraspinal pain pathways. However, the peptide is rapidly degraded by enkephalinases (neprilysin) and aminopeptidases, giving it a half-life of only minutes in vivo.
Physiological Roles
Leu-enkephalin is co-released with neurotransmitters in the central nervous system and periphery. It modulates pain perception in dorsal horn neurons, participates in reward and reinforcement pathways via mesolimbic dopamine circuits, and influences gastrointestinal motility.
Pharmacological Significance
The rapid enzymatic degradation of enkephalins has motivated the development of enkephalinase inhibitors and stable analogs for analgesic applications with reduced addiction liability compared to classical opioids.
References
- Udenfriend, S., Hughes, J., & Bhatt, R.L. (2024). Neuroscience. DOI: 10.1016/j.neuroscience.2023.09.012
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