[Leu5]-enkephalin

• CAS: 58822-25-6
• Catalog Number: ACM58822256
• Category: Main Products
• Molecular Weight: 555.62
• Molecular Formula: C₂₈H₃₇N₅O₇
• Synonyms: L-TYR-GLY-GLY-PHE-LEU;LEUCINE-ENKEPHALIN (HUMAN, PORCINE, BOVINE, RAT, MOUSE);LEUCINE-ENKEPHALIN (HUMAN, PORCINE, BOVINE, RAT, MOUSE) H₂O;LEUCINE-ENKEPHALIN;LEU-ENKEPHALIN;[LEU5]-ENKEPHALIN;ENKEPHALIN, LEU5-, HUMAN;ENKEPHALIN L
• IUPAC Name: [LEU5]-ENKEPHALIN
• Boiling Point: 998.8ºC at 760 mmHg
• Flash Point: 557.8ºC
• Density: 1.274 g/cm³
• Appearance: solid
• Exact Mass: 555.26900
• Safety Description: 22-24/25
• WGK Germany: 3

Case Study

[Leu5]-enkephalin as a Substrate for Investigating Spinal Antinociception under Peptidase Inhibition

Miura, Masaaki, et al. Tokai J Exp Clin Med 38.2 (2013): 62-70.

[Leu5]-enkephalin (LE), an endogenous opioid pentapeptide, produces potent antinociceptive effects but undergoes rapid enzymatic degradation by multiple peptidases, including aminopeptidase N (APN), angiotensin-converting enzyme (ACE), and neutral endopeptidase (NEP). This limits its analgesic efficacy in vivo. This study evaluated the antinociceptive effect of intrathecally administered LE in rats pretreated with combinations of peptidase inhibitors: amastatin (APN inhibitor), captopril (ACE inhibitor), and phosphoramidon (NEP inhibitor).
Methods: Male Wistar rats with intrathecal catheters received LE alone or following pretreatment with single, dual, or triple inhibitor combinations. Antinociception was assessed using the tail-flick test, with percent maximal possible effect (%MPE) and area under the curve (AUC) calculated.
Key Results:
· Pretreatment with the triple inhibitor combination (10 nmol each) increased the antinociceptive potency of LE by >100-fold: 10 nmol LE + inhibitors produced an effect equivalent to 1000 nmol LE alone.
· Triple inhibitor pretreatment dose-dependently enhanced LE (10 nmol) antinociception, with significant potentiation at 3, 10, and 30 nmol inhibitor doses.
· Any single inhibitor (amastatin, captopril, or phosphoramidon) significantly increased LE-induced antinociception compared to saline pretreatment, but the effect was markedly smaller than with the triple combination.
· All dual inhibitor combinations (amastatin+captopril, amastatin+phosphoramidon, captopril+phosphoramidon) produced significantly lower antinociception than the triple combination, indicating that any residual single peptidase activity still inactivates substantial amounts of LE.

[Leu5]-enkephalin as a Model Peptide for Organometallic Modification to Enhance Blood-Brain Barrier Permeation

Pinto, Antonio, et al. ChemBioChem 10.11 (2009): 1852-1860.

[Leu5]-enkephalin (LE) exhibits analgesic activity but suffers from poor blood-brain barrier (BBB) penetration due to rapid enzymatic degradation and low lipophilicity. This study investigated the conjugation of LE with organometallic compounds-specifically ferrocene carboxylic acid and cobaltocenium carboxylic acid-to enhance BBB permeation while maintaining low cytotoxicity. LE derivatives were synthesized via solid-phase peptide synthesis, incorporating metallocenoyl groups at the N-terminus. Fluorescein-labeled analogues were prepared for cellular uptake studies.
Key Results:
· N-terminal ferrocenoylation of LE (compound 3) increased logP from -1.20 (unmodified LE) to 5.79, exceeding even free ferrocene (logP ≈ 3.1). Cobaltocenium modification (4) yielded logP = 2.18, reflecting its positive charge.
· BBB permeation coefficients (Papp) in the PBCEC model correlated with lipophilicity: ferrocenoyl-LE (3) showed the highest Papp, a 1.8-fold increase over unmodified LE. Acetylated LE (2) and cobaltocenium-LE (4) gave intermediate values.
· Fluorescence microscopy revealed significantly enhanced cellular uptake of ferrocenoyl-fluorescein-LE (6) compared to non-metallated controls (5, 8, 9) in HeLa and HepG2 cells after 24 h incubation. Uptake was less pronounced in HT-29 cells, possibly due to their extracellular matrix.
· Cytotoxicity assays showed that compounds 3 and 4 were non-toxic up to 1 mM in all three cell lines, with >80% viability maintained. Reduced viability was observed only at ≥750 μM, indicating a favorable safety margin.

Custom Q&A

What is the molecular formula of [Leu5]-enkephalin?

The molecular formula of [Leu5]-enkephalin is C28H37N5O7.

What are the synonyms of [Leu5]-enkephalin?

The synonyms of [Leu5]-enkephalin include Leu-enkephalin, leucine enkephalin, and Enkephalin.

What is the molecular weight of [Leu5]-enkephalin?

The molecular weight of [Leu5]-enkephalin is 555.6 g/mol.

How is [Leu5]-enkephalin produced in vertebrate species?

[Leu5]-enkephalin is produced in vertebrate species through the decomposition of proenkephalin or dynorphin.

What properties does [Leu5]-enkephalin exhibit?

[Leu5]-enkephalin exhibits antinociceptive properties and acts as a delta-opioid receptor agonist, a mu-opioid receptor agonist, a neurotransmitter, an analgesic, a human metabolite, and a rat metabolite.

What is the role of [Leu5]-enkephalin?

The role of [Leu5]-enkephalin is as an endogenous opioid peptide with morphine-like activity.

How does [Leu5]-enkephalin differ from Met-enkephalin?

[Leu5]-enkephalin differs from Met-enkephalin in the leucine residue at position 5.

What is the first four amino acid sequence of [Leu5]-enkephalin identical to?

The first four amino acid sequence of [Leu5]-enkephalin is identical to the tetrapeptide sequence at the N-terminal of beta-endorphin.

What is the IUPAC name of [Leu5]-enkephalin?

The IUPAC name of [Leu5]-enkephalin is (2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoic acid.

What is the CAS number of [Leu5]-enkephalin?

The CAS number of [Leu5]-enkephalin is 58822-25-6.