Enkephalin
Enkephalin — A pentapeptide (Met-enkephalin or Leu-enkephalin) that binds opioid receptors, studied as an endogenous pain-modulating neuropeptide.
What Are Enkephalins?
Enkephalins are pentapeptide opioids existing in two forms: Met-enkephalin (Tyr-Gly-Gly-Phe-Met, MW: 573.66 Da) and Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu, MW: 555.63 Da). Discovered by John Hughes and Hans Kosterlitz in 1975, they were the first endogenous opioid peptides identified and demonstrated that the brain produces its own morphine-like substances.
Mechanism of Action
Enkephalins preferentially bind delta-opioid receptors (DOR) with moderate affinity for mu-opioid receptors (MOR). The N-terminal Tyr-Gly-Gly-Phe "message" sequence is shared with all opioid peptides and is essential for receptor binding. The 5th residue (Met or Leu) modulates receptor subtype selectivity.
Research Significance
- Opioid pharmacology: Enkephalins established the concept of endogenous opioid ligands and led to receptor subtype classification
- Pain modulation: Released from interneurons in the spinal dorsal horn for local pain inhibition
- Peptide stability: Their extremely short half-life (< 2 minutes due to enkephalinase) drove development of protease-resistant peptidomimetic opioids
- DALA enkephalin: [D-Ala2]-Met-enkephalin was among the first D-amino acid substituted peptides, proving the strategy extends half-life
Frequently Asked Questions
What is Enkephalin?
A pentapeptide (Met-enkephalin or Leu-enkephalin) that binds opioid receptors, studied as an endogenous pain-modulating neuropeptide.
Why is Enkephalin important in peptide research?
Enkephalin is a fundamental concept in compound as it relates to peptide science. It directly influences experimental design, compound characterization, and the reliability of research outcomes across biochemistry and molecular biology disciplines.