[Leu5]-Enkephalin

[Leu5]-Enkephalin is a pentapeptide endogenous opioid involved in nociception, pain modulation, and neurochemical signaling. Along with Met-enkephalin, it is derived from the proenkephalin gene and acts mainly through δ-opioid receptors. Enkephalins regulate pain perception, stress responses, mood, and reward-associated neurotransmission. [Leu5]-Enkephalin is widely used in neuroscience and pharmacology research to investigate opioid receptor function, endogenous analgesic mechanisms, receptor selectivity, neuropeptide signaling, and pathways involved in mood regulation and pain processing. This peptide is valuable for studies of opioid biology and endogenous pain-control systems.

Product Name: [Leu5]-Enkephalin

Sequence One Letter Code: YGGFL

Sequence Three Letter Code: H-Tyr-Gly-Gly-Phe-Leu-OH

Cas No: 58822-25-6

Chemical Formula:C28H37N5O7

Molecular Weight: 555.7

Purity: ≥ 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)CNC(=O)[C@H](CC2=CC=C(C=C2)O)N

SMILES: (2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoic acid

IUPAC: URLZCHNOLZSCCA-VABKMULXSA-N

INCHIKEY: InChI=1S/C28H37N5O7/c1-17(2)12-23(28(39)40)33-27(38)22(14-18-6-4-3-5-7-18)32-25(36)16-30-24(35)15-31-26(37)21(29)13-19-8-10-20(34)11-9-19/h3-11,17,21-23,34H,12-16,29H2,1-2H3,(H,30,35)(H,31,37)(H,32,36)(H,33,38)(H,39,40)/t21-,22-,23-/m0/s1

Source / Species: 

Conjugation: Unconjugated

Code Nacres:NA.26

Current Research: [Leu5]-Enkephalin, also called Leu-enkephalin, is an endogenous opioid pentapeptide with the sequence Tyr-Gly-Gly-Phe-Leu. It belongs to the enkephalin family of opioid peptides and was among the earliest endogenous opioid ligands identified in mammalian nervous tissue. Current reference summaries describe Leu-enkephalin as a five-amino-acid endogenous peptide that acts as an opioid receptor agonist and preferentially binds δ-opioid receptors while also showing activity at μ-opioid receptors. Current research on [Leu5]-Enkephalin focuses on opioid receptor pharmacology, pain modulation, mood and stress responses, neuroendocrine signaling, receptor trafficking, and peptide analog development. Enkephalins are derived from larger precursor proteins, especially proenkephalin, through post-translational proteolytic processing. Their short Tyr-Gly-Gly-Phe opioid “message” sequence is essential for interaction with opioid receptors. The leucine residue at position 5 distinguishes Leu-enkephalin from Met-enkephalin and can influence receptor preference, enzymatic degradation, and analog design. A major application is δ-opioid receptor research. Leu-enkephalin is often used as a native ligand or reference agonist for studying δ-opioid receptor activation. δ-opioid receptors are involved in pain modulation, mood regulation, neuroprotection, emotional behavior, learning, and stress adaptation. Researchers use Leu-enkephalin in receptor binding assays, G protein activation assays, cAMP inhibition assays, β-arrestin recruitment assays, receptor internalization studies, ERK phosphorylation assays, and opioid antagonist competition experiments. Leu-enkephalin is also relevant to μ-opioid receptor biology. Although it is often considered more δ-preferring than μ-selective, it can activate μ-opioid receptors depending on assay system, receptor expression, and peptide concentration. This makes it useful for comparing endogenous opioid peptide signaling with synthetic opioid agonists and for evaluating receptor subtype selectivity. Product data report agonist activity at δ-, μ-, and weaker κ-opioid receptor systems in transfected cell assays, illustrating its broad but preferential opioid receptor activity profile. Pain research remains a central use. Enkephalins are present throughout nociceptive pathways, including peripheral tissues, spinal cord, and brain. They modulate pain transmission by reducing neurotransmitter release, hyperpolarizing neurons, and altering pain-related circuits. Leu-enkephalin can be used to study endogenous analgesia, inflammatory pain, neuropathic pain, descending inhibition, spinal opioid signaling, and peripheral opioid mechanisms. Leu-enkephalin is also important in peptide stability and metabolism research. Native enkephalins are rapidly degraded by peptidases, including aminopeptidases, neprilysin, and other extracellular enzymes. This short half-life has driven the design of stable enkephalin analogs, peptidomimetics, D-amino-acid substitutions, cyclized peptides, and enzyme-resistant derivatives. Research exploring enkephalin backbone modification has shown that structural changes can preserve biological activity while altering receptor signaling and stability. In neuroprotection research, many studies use modified Leu-enkephalin analogs such as DADLE to explore δ-opioid receptor-mediated cytoprotection during ischemia or oxygen-glucose deprivation. Although DADLE is not native Leu-enkephalin, these analog studies help clarify how Leu-enkephalin-derived opioid pharmacophores can influence neuronal survival, mitochondrial function, and ischemic injury pathways. Leu-enkephalin is also useful in analytical chemistry. It is frequently used as a peptide standard in mass spectrometry because of its defined sequence, small size, and stable ionization behavior. Researchers use it for instrument calibration, peptide fragmentation studies, LC-MS method development, and opioid peptide quantification workflows. In behavioral and neuroendocrine research, Leu-enkephalin supports studies of stress adaptation, reward, emotion, movement, endocrine regulation, and autonomic function. Because endogenous opioid systems interact with dopamine, CRF, oxytocin, and other neuropeptide networks, Leu-enkephalin can be used to probe cross-talk between pain, stress, mood, and reward circuits. Overall, [Leu5]-Enkephalin is a foundational endogenous opioid peptide for neuroscience and pharmacology research. It supports studies of δ- and μ-opioid receptor signaling, pain modulation, endogenous analgesia, receptor selectivity, peptide degradation, neuroprotection, neuroendocrine regulation, and opioid peptide analog development. Its compact pentapeptide structure makes it a practical and highly relevant reference ligand for opioid peptide biology.