[Leu5]Enkephalin | CAS 58822-25-6 | Endogenous Opioid Receptor Agonist (Research Use Only) | Knowlux

Product Description

[Leu5]Enkephalin, CAS 58822-25-6, is a synthetic pentapeptide corresponding to the leucine-enkephalin sequence, one of the two principal endogenous opioid peptides discovered in mammalian brain, supplied by Knowlux for laboratory research use. The sequence is H-Tyr-Gly-Gly-Phe-Leu-OH, a linear pentapeptide with a free N-terminal tyrosine and a free C-terminal leucine carboxylate. The molecular formula is C28H37N5O7 and the molecular weight is 555.62 g/mol. Unlike Dynorphin A (1-13), which is the prototypical kappa receptor agonist in this catalogue, [Leu5]Enkephalin is the prototypical delta/mu opioid receptor agonist, and the pharmacological contrast between the two endogenous opioid peptides is a central reason both are maintained as reference tools. Each lot is released with a lot-specific COA, MSDS and analytical traceability.

CAS and Salt Form Clarification: CAS 58822-25-6 is the free peptide registry for [Leu5]Enkephalin and is the identifier applied across MedChemExpress, InvivoChem, Biorbyt, AbMole, and ChemicalBook. Two related but distinct salt/derivative registries circulate in commercial listings and must not be conflated with the free peptide. The trifluoroacetate salt is registered under CAS 73563-78-7, with formula C30H38F3N5O9 and MW 669.65, as listed by MedChemExpress for its [Leu5]-Enkephalin TFA catalogue item. The C-terminal amide derivative is registered under CAS 60117-24-0, with formula C28H38N4O6 and MW 554.64, as listed by MedChemExpress and BZWZ-China. A supplier entry also lists a [Leu5]-Enkephalin acetate under CAS 81678-16-2 with the formula C28H37N5O7.xC2H4O2, which is a third distinct registry that should not be substituted for 58822-25-6 without COA confirmation. Knowlux specifies the salt or derivative form, counter-ion identity, and counter-ion content per lot on the COA. Buyers should confirm whether the quoted material is free peptide, TFA salt, acetate salt, or the C-terminal amide before procurement, as the TFA counter-ion alone adds approximately 114 g/mol to the free-peptide mass.

Structural and Metabolic Note: [Leu5]Enkephalin is the shortest of the endogenous opioid peptides at five residues. Its N-terminal Tyr-Gly-Gly-Phe tetrapeptide is the conserved opioid message sequence shared with [Met5]Enkephalin and dynorphin A, but the C-terminal leucine in place of methionine is the single substitution that distinguishes the two enkephalins and contributes to their differing receptor selectivity profiles. The peptide is highly susceptible to peptidase degradation in biological matrices; the free N-terminal tyrosine and the Gly-Gly-Phe segment are the principal sites of aminopeptidase and dipeptidyl aminopeptidase cleavage, and this metabolic lability is a key reason why synthetic enkephalin analogues rather than the native peptide are used in many in vivo studies. Unlike the disulfide-constrained peptides in the Linaclotide and Plecanatide families, [Leu5]Enkephalin is linear and contains no cysteine; unlike the methionine-containing peptides in the Nesiritide and Ularitide families, it contains no methionine and therefore has no methionine sulfoxide oxidation liability. The sole aromatic residues are Tyr1 and Phe4.

Product Parameters

Product Details

1. Overview

[Leu5]Enkephalin (leucine-enkephalin) is an endogenous pentapeptide opioid neurotransmitter first isolated from mammalian brain and adrenal medulla. It is one of the two enkephalins, alongside [Met5]Enkephalin, and it is derived from the proenkephalin precursor. Enkephalins are concentrated in the spinal dorsal horn, where they participate in pain modulation, and in limbic and striatal regions, where they influence motivation, reward, and motor control. [Leu5]Enkephalin is widely used as a reference agonist in opioid receptor pharmacology, as a substrate in peptidase degradation studies, and as a comparator against synthetic enkephalin analogues designed for improved metabolic stability. The material supplied under this specification is research-grade and is not intended for human administration.

2. Receptor Pharmacology and Selectivity

[Leu5]Enkephalin is an agonist at both delta and mu opioid receptors, with a slight preference for the delta subtype. Biorbyt and TargetMol both report Ki values of 4.0 nM for the delta-opioid receptor and 3.4 nM for the mu-opioid receptor, giving a delta/mu Ki ratio of approximately 1.2, which is functionally close to non-selective across the two subtypes. The BindingDB and Guide to Pharmacology literature contain additional values that illustrate the assay-dependent spread: MedChemExpress cites a Kf of 18.9 nM for a non-mammalian opioid receptor in its background section, and a comparative binding table in Molecular Medicine reports a Ki of 835 nM for [Leu5]Enkephalin at the kappa receptor, which is approximately 200-fold weaker than its delta/mu affinity and establishes the peptide as delta/mu-preferring with negligible kappa engagement at physiological concentrations. This selectivity profile is the mirror image of Dynorphin A (1-13) in this catalogue, which is kappa-preferring, and the two peptides are therefore complementary tools for dissecting opioid receptor subtype contributions in mixed-expression systems.

The distinction between delta/mu-preferring enkephalins and kappa-preferring dynorphins is well established in the endogenous opioid literature: MedChemExpress background section states that enkephalins are the putative endogenous ligands for the delta receptor, whereas dynorphins are the endogenous ligands for the kappa receptor. Researchers designing selectivity panels should note that [Leu5]Enkephalin delta/mu ratio of approximately 1.2 means it does not cleanly discriminate between these two subtypes; the more delta-selective synthetic analogue D-Ala2-D-Leu5-enkephalin (DADLE) or the more mu-selective D-Ala2-N-Me-Phe4-Gly-ol5-enkephalin (DAMGO) are the appropriate tools where subtype discrimination is the experimental objective. These values are assay- and system-dependent and are provided for scientific reference only.

3. Research Applications

Published pharmacological characterizations and documented protocols describe the following research applications:

• Delta and mu opioid receptor binding and functional agonist assays (radioligand displacement, GTPgammaS binding)

• Endogenous opioid peptide pharmacology and comparative selectivity profiling against [Met5]Enkephalin and Dynorphin A (1-13)

• Pain modulation and antinociception research models (spinal and supraspinal administration)

• Enkephalinase (neutral endopeptidase, aminopeptidase N) inhibition and peptide metabolism studies

• Neuropeptide release and turnover studies in brain slice and synaptosome preparations

• Reference standard development for HPLC and LC-MS analytical methods

These descriptions are derived from published research and are provided for scientific reference only.

Quality Control

Solubility and Handling

Solubility: [Leu5]Enkephalin solubility is high in DMSO and more variably reported in water, and the divergence is larger for the aqueous value than for most peptides in this catalogue. MedChemExpress reports DMSO 116.67 mg/mL (209.98 mM, ultrasonic) and PBS 6.67 mg/mL (12.00 mM, clear solution with sonication). InvivoChem, Biorbyt, AbMole, and MolCore report DMSO >=150 mg/mL (269.97 mM, ultrasonic) and H2O ~100 mg/mL (179.98 mM, ultrasonic). ChemicalBook lists an additional set of values from a supplier batch: >=54.6 mg/mL in H2O, >=54.8 mg/mL in EtOH, and >=55.6 mg/mL in DMSO, alongside a second entry stating soluble in water (1 mg/mL). Tocris lists solubility to 1 mg/mL in water. The ~100 mg/mL and ~1 mg/mL aqueous figures differ by two orders of magnitude and likely reflect different salt forms, lot histories, and whether the measurement was performed with ultrasonic assistance on a saturated solution. For practical stock preparation, DMSO at >=150 mg/mL is the most consistently supported condition, and water at ~100 mg/mL is achievable with sonication on lots that have not been supplied as a less-soluble salt form. Prepare solutions fresh and aliquot to avoid repeated freeze-thaw cycles; MedChemExpress specifies that stock solutions are stable for 6 months at -80C or 1 month at -20C under sealed, moisture-free conditions.

Handling Precautions: Use powder-handling containment (glove box or fume hood with particulate control). Avoid inhalation of fine powder. Wear nitrile gloves, lab coat, and eye protection. Because the peptide contains no cysteine or methionine, reducing agents and oxidation-protection measures are not required. The lyophilized powder is hygroscopic; equilibrate vials to room temperature before opening.

Storage and Stability

Documentation Support

Per lot: COA, MSDS, HPLC chromatogram, and mass spectrometry data. Salt or derivative form, counter-ion identity, and counter-ion content available on request. Custom specifications and third-party inspection can be arranged on a project basis.

About Knowlux

Knowlux Biotechnology is a GMP-oriented manufacturer and supplier of peptides, APIs and fine-chemical research compounds, operating from Hubei, China. We serve research groups, CDMOs and distributors in more than 40 countries, and support contract synthesis, custom packaging and technical documentation requests.

Compliance Statement

FOR RESEARCH USE ONLY. NOT FOR HUMAN USE. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE.

This product is supplied for laboratory research use only. It is not for human or animal administration, not for diagnostic or therapeutic use, not for retail sale, and not for personal use. [Leu5]Enkephalin is not approved as a medicinal product in any jurisdiction. The purchaser is responsible for verifying product specifications against their specific research requirements and for compliance with all applicable institutional, local, and national regulations governing research chemical acquisition, storage, and use. Research context statements are for scientific reference only and do not constitute medical advice, promotional claims, or dosing guidance.

Data Verification Notes

The molecular formula C28H37N5O7 and molecular weight 555.62 are confirmed across MedChemExpress, InvivoChem, Biorbyt, AbMole, Adooq, and GenScript. The sequence Tyr-Gly-Gly-Phe-Leu is confirmed by MedChemExpress, Adooq, BOC Sciences, GenScript, and Biozol. The TFA salt CAS 73563-78-7, formula C30H38F3N5O9, and MW 669.65 are from MedChemExpress [Leu5]-Enkephalin TFA datasheet. The C-terminal amide CAS 60117-24-0, formula C28H38N4O6, and MW 554.64 are from MedChemExpress and BZWZ-China. The acetate registry 81678-16-2 is from a Catorm listing; the formula field there is rendered as C28H37N5O7.xC2H4O2 and is noted for completeness but not adopted as a primary identifier. The delta/mu Ki values (4.0 nM and 3.4 nM) are from Biorbyt and TargetMol; the kappa Ki of 835 nM is from the Molecular Medicine comparative table. The Kf of 18.9 nM is from MedChemExpress background section and refers to a non-mammalian receptor, as indicated by the context in which it appears. Solubility values are reported with their source conditions rather than reconciled into a single figure because the aqueous data span 1 mg/mL to ~100 mg/mL and reflect different salt forms, lot histories, and dissolution techniques. Storage shelf-life divergence (-20C versus -80C for powder; 6 months versus 1 year versus 2 years for solutions) is reported as-is; the -20C powder condition is the most widely supported archival temperature, and -80C is presented as the conservative option.

Formatting Note: All formulas, sequences, and comparison operators use plain ASCII notation to prevent character corruption on the platform. Section headings, table alignment, and spacing follow the approved product detail pattern. No trailing spaces or non-breaking characters are used; tables use consistent pipe alignment.