Pentapeptide-18 (Leuphasyl)

🧪 What Is Pentapeptide-18 (Leuphasyl®)?

Pentapeptide-18 (INCI name; trade name Leuphasyl®) is a synthetic pentapeptide analog of methionine-enkephalin, an endogenous opioid neuropeptide involved in pain modulation and neurotransmitter regulation .

This is NOT a collagen-stimulating matrix peptide. Unlike Pal-GHK or Pal-KTTKS, which target fibroblast extracellular matrix synthesis, Pentapeptide-18 is a neuroactive peptide specifically engineered to interact with enkephalin receptors on neuronal cell membranes .

Structural Uniqueness & Rational Design:

• Sequence: Tyr-D-Ala-Gly-Phe-Leu-OH
• The incorporation of D-Alanine at position 2 (versus Glycine in native enkephalin) confers significant proteolytic resistance to aminopeptidases, extending the peptide’s functional half-life in experimental systems .
• C-terminal leucine (vs. methionine in met-enkephalin) provides enhanced chemical stability, eliminating oxidation risk associated with methionine sulfoxide formation.

This is the ENKEPHALIN ANALOG—not to be confused with enkephalin-inhibiting peptides or unrelated pentapeptides.

⚠️ STRICT RESEARCH USE ONLY: Not for human consumption, injection, topical application, or cosmetic formulation. For in vitro and ex vivo laboratory experimentation exclusively.

⚗️ Pentapeptide-18: Verified Technical Specifications

Precision neuropharmacology demands reagents of verified identity, defined stereochemistry, and documented purity. Below is the complete analytical profile for our Pentapeptide-18. Every batch is accompanied by a lot-specific Certificate of Analysis (COA) with raw HPLC chromatograms and MS spectra. 📊✅

📋 Peptide Specifications Table

🔬 How Does Pentapeptide-18 Work? Molecular Mechanisms & Neuronal Signaling

Pentapeptide-18 operates via a GPCR-mediated neuromodulatory mechanism fundamentally distinct from other cosmetic peptides .

1. 🧲 Enkephalin Receptor Binding (Opioid Pathway)

Pentapeptide-18 functions as a peptidic enkephalin mimetic:

• Target: δ-opioid receptors (DOR) and, to a lesser extent, μ-opioid receptors (MOR) on neuronal cell membranes
• Binding event: Competitive agonism at the orthosteric binding site
• Consequence: Receptor conformational change → G protein activation

2. ⚡ Intracellular Signaling Cascade

Upon receptor binding, Pentapeptide-18 triggers:

1. G⍺i subunit activation: Inhibition of adenylyl cyclase → ↓ cAMP → ↓ PKA activity
2. Gβγ subunit-mediated signaling: Direct modulation of voltage-gated calcium channels (VGCCs; Cav2.2) → channel closure
3. Potassium channel opening: GIRK (G protein-coupled inwardly-rectifying potassium channels) → membrane hyperpolarization

3. 🧪 Functional Outcome: Neurotransmitter Release Modulation

The combined effect is reduced neuronal excitability and suppressed exocytotic neurotransmitter release:

• Acetylcholine (ACh): Primary target at neuromuscular junctions
• Glutamate: Documented reduction in glutamatergic neuron cultures
• Catecholamines: Norepinephrine, dopamine (context-dependent)

📌 Critical Research Note: Pentapeptide-18 does NOT block acetylcholine receptors (nAChRs, mAChRs). It modulates presynaptic release probability. This is a fundamentally different mechanism from botulinum neurotoxins (enzymatic SNARE cleavage) and argireline (SNARE complex inhibition).

🧫 Primary Research Applications & Typical Research Focuses

Pentapeptide-18 is not a “wrinkle cream ingredient” in our supply chain—it is a precision neuropharmacology tool. Below are the validated experimental models:

🧠 1. Neuropharmacology & Opioid Receptor Research

• δ-opioid receptor (DOR) agonism assays: cAMP inhibition (Glosensor®), β-arrestin recruitment (Tango®)
• Receptor binding competition: [³H]-DADLE or [³H]-naloxone displacement
• Functional selectivity (biased agonism) studies: G protein vs. β-arrestin bias factor calculation

🔬 2. Neuromuscular Junction & Synaptic Transmission

• Primary neuronal culture: Hippocampal or cortical neurons; whole-cell patch clamp recording of mEPSCs/miniature postsynaptic currents
• Neuromuscular junction (NMJ) explants: Phrenic nerve-hemidiaphragm preparation (rodent); quantal content analysis
• Calcium imaging: Fluo-4/AM; depolarization-evoked Ca²⁺ influx

🧪 3. Analgesia & Pain Pathway Research

• In vitro nociceptor models: Dorsal root ganglion (DRG) neurons; capsaicin- or KCl-evoked CGRP release
• Opioid tolerance studies: Chronic vs. acute exposure paradigms

💊 4. Peptidase Resistance & Stability Studies

• Aminopeptidase degradation kinetics: Incubation with leucine aminopeptidase (LAP); HPLC monitoring of D-Ala vs. Gly variants
• Plasma stability assays: Human/rat plasma; t½ determination

📄 Certificate of Analysis (COA) & Quality Verification Protocol

Why “≥98%” Is Essential for Neuropeptide Research. 🎯

Pentapeptide-18 contains a non-native D-amino acid (D-Ala) , which presents unique synthetic and analytical challenges. Lower-purity sources (<95%) frequently contain:

• L-Ala epimers → D-Ala to L-Ala racemization → altered receptor binding affinity
• Deletion sequences (Tyr-D-Ala-Gly-Phe-OH) → partial agonism/antagonism
• Oxidation products (unlikely here; no Met/Trp/Cys) but sequence fidelity issues

Our ≥98% specification eliminates these variables. 🔬✅

📈 High Performance Liquid Chromatography (HPLC)

• Instrument: Waters Alliance e2695 / Agilent 1260 Infinity II
• Column: C18, 5 µm, 4.6 × 250 mm
• Mobile phase: 0.1% TFA in H₂O (A) / 0.1% TFA in acetonitrile (B)
• Gradient: 10–40% B over 25 min
• Detection: PDA @ 214 nm (peptide bonds) & 280 nm (tyrosine)
• Acceptance Criteria: Main peak area ≥98.0% ; resolution of D-Ala vs. L-Ala variants ≥1.5

🎯 Mass Spectrometry (MS)

• Method: ESI-TOF (Electrospray Ionization Time-of-Flight), positive mode
• Expected [M+H]⁺: 570.65 m/z
• Expected [M+2H]²⁺: 285.83 m/z
• Expected [M+Na]⁺: 592.63 m/z
• Acceptance Criteria: Mass accuracy ±0.5 Da ; confirm presence of D-Ala signature (distinct retention time from L-Ala variant)

🧬 Amino Acid Analysis (AAA)

• Method: HCl hydrolysis (110°C, 24 hr); pre-column derivatization; RP-HPLC
• Expected ratios: Tyr (1.0), Ala (1.0), Gly (1.0), Phe (1.0), Leu (1.0)
• Acceptance Criteria: All residues within ±10% of theoretical

💧 Additional QC Parameters

• Appearance: Visual inspection—white, free-flowing powder
• Solubility test: Clear solution in water at 10 mg/mL
• Bulk density: Consistent with lyophilized cake integrity
• Residual solvents: GC headspace; complies with ICH Q3C

Your downloadable COA includes: Annotated HPLC chromatogram (integration markers, impurity profiling), raw MS spectra (annotated adduct peaks), AAA stoichiometry table, and QC Manager digital signature. We actively encourage independent third-party verification. 🛡️

❓ Frequently Asked Questions (FAQs)

1. Is Pentapeptide-18 the same as Pentapeptide-3 (Vialox)?

NO. This is a critical and common error. 🚫

• Pentapeptide-18 (Leuphasyl®): CAS 64963-01-5; Sequence Tyr-D-Ala-Gly-Phe-Leu-OH; MW 569.65; Enkephalin analog; Opioid receptor agonist
• Pentapeptide-3 (Vialox®): CAS 135679-88-8 (approx); Sequence Gly-Pro-Arg-Ile-Ala-OH; MW ~500; nAChR antagonist; Completely different mechanism
• They are NOT interchangeable. Verify CAS number against COA immediately.

2. What is “D-Ala” and why is it important?

D-Ala = D-Alanine. It is a non-proteinogenic, dextrorotatory amino acid enantiomer.

• Native enkephalin has Glycine at position 2 → rapidly cleaved by aminopeptidases
• D-Ala substitution → proteolytically resistant → extended experimental half-life
• Critical QC parameter: Must verify absence of L-Ala (racemization) via chiral chromatography or retention time matching

3. Is Pentapeptide-18 water-soluble?

YES. Unlike acylated lipopeptides (Pal-GHK, Pal-Di-6), Pentapeptide-18 is freely soluble in aqueous buffers.
Reconstitution protocol:

1. Centrifuge vial briefly (ensures pellet at bottom).
2. Add sterile water, PBS (pH 7.4), or cell culture media (5–10 mg/mL).
3. Vortex gently 30–60 seconds until optically clear.
4. Use immediately or aliquot and freeze at -20°C.

4. What purity do I need for opioid receptor binding assays?

≥98% is mandatory. Lower-purity batches often contain:

• L-Ala epimers → reduced DOR affinity → false-negative potency estimates
• Des-Tyr truncation (D-Ala-Gly-Phe-Leu-OH) → inactive → overestimates required concentration
• Acetylated species (Ac-Tyr-D-Ala-…) → reduced activity

5. How stable is reconstituted Pentapeptide-18?

• Lyophilized powder: 24 months at -20°C (desiccated)
• In sterile water/PBS: 1 month at -20°C (single-use aliquots)
• At 4°C: <7 days (risk of bacterial growth; peptide stable but solution not sterile)
• At room temperature: <24 hours
• Discard unused working solution. Do NOT refreeze.

6. What is the synergistic effect with Acetyl Hexapeptide-3?

Pentapeptide-18 and Acetyl Hexapeptide-3 (Argireline®) target distinct molecular nodes in the neuromuscular signaling cascade :

• Pentapeptide-18: Presynaptic (↓ neurotransmitter release probability)
• Argireline: Postsynaptic/SNARE (↓ vesicle docking/fusion)
• Result: Synergistic inhibition in co-treatment models

📦 Packaging, Shipping & Laboratory Handling

📦 Packaging Specifications

• Primary container: 2 mL or 5 mL Type I borosilicate glass vial (USP/EP certified)
• Closure: Bromobutyl rubber stopper (low heavy-metal, latex-free), aluminum crimp seal
• Headspace: Nitrogen-purged to prevent oxidative degradation
• Secondary packaging: Foil laminate zip-seal bag with indicating desiccant (cobalt-free)

🚚 Shipping Conditions (USA Domestic)

• Carrier: FedEx Priority Overnight / 2Day
• Thermal protection: Ambient shipping (stable at room temperature); ice packs available upon request for warm climates
• Transit time: 2–5 business days (contiguous USA)
• International: FedEx International Priority; buyer responsible for local duties/taxes/import permits

🧤 Laboratory Handling & Safety

• PPE required: Nitrile gloves, lab coat, safety eyewear
• Ventilation: Standard laboratory ventilation sufficient
• Decontamination: 70% ethanol
• Spill management: Absorb with inert material; dispose as chemical waste

🛡️ Why Choose Buy Peptides Online USA? (Transactional Value Proposition)

We do not sell “cosmetic ingredients.” We supply analytically verified research reagents to qualified laboratories. Here is why experienced neuropharmacology investigators choose us—and keep choosing us: 🏆

✅ Authenticity Guarantee (No Fine Print)

If the HPLC/MS/AAA data does not match the stated specifications, you receive:

• Full replacement (expedited, 2-day air) OR
• 100% refund (no restocking fee, no return shipping cost)

🔬 Technical Consultation (24/7)

Our support team consists of scientists who understand peptide chemistry AND neuropharmacology.

• Not chatbots. Not script readers.
• Ask about: D-Ala racemization, opioid receptor assay design, solubility in specialized buffers
• Response time: <2 hours (business hours); <12 hours (after hours)

💰 Flexible Payment Options

• Credit cards: VISA, MC, AMEX, Discover (Stripe PCI-DSS Level 1)
• Cryptocurrency: Bitcoin, Ethereum, USDT (ERC-20/Tron) → +5% discount
• Bank wire: Available for institutional purchase orders (NET 15 for qualified academic institutions)

📦 Rapid Fulfillment

• Same-day shipping for orders placed before 2:00 PM EST (Mon–Fri)
• Real-time inventory—no backorders on in-stock items
• Bulk quotes available for >1 gram quantities

🧪 Research-Exclusive Supply Chain

We do not sell to consumers. We do not support cosmetic formulation. Our systems, labeling, disclaimers, and compliance protocols are optimized exclusively for the laboratory research community. 🔬🇺🇸

📚 Referenced Citations & Scientific Background

The following peer-reviewed and technical literature supports the research applications and specifications described above:

1. CAS Common Chemistry. (2025). Pentapeptide-18 (64963-01-5). American Chemical Society.
2. Blanes-Mira, C., et al. (2022). A comparative analysis of Pentapeptide-18 and other neurotransmitter-inhibiting peptides in cosmetic applications. International Journal of Cosmetic Science, 44(2), 178-186.
3. Park, J., et al. (2020). D-tyrosine-modified Pentapeptide-18 suppresses melanogenesis. Scientific Reports, 10(1), 262.
4. Wang, Y., et al. (2023). Molecular mechanisms of Pentapeptide-18: Neuromuscular junction modulation. Journal of Investigative Dermatology, 143(1), 55-63.
5. Rodriguez, P., et al. (2021). Clinical evaluation of Pentapeptide-18 in combination with other peptides. American Journal of Clinical Dermatology, 22(4), 512-521.
6. Johnson, A., et al. (2022). Optimizing peptide delivery systems: Pentapeptide-18 formulation. Journal of Controlled Release, 341, 230-242.
7. Zhang, H., et al. (2023). Comparative efficacy of Pentapeptide-18 versus injectable neurotoxins. Plastic and Reconstructive Surgery, 151(3), 554-563.
8. MOL Changes. (2025). Pentapeptide-18 Technical Data Sheet.
9. BenchChem. (2024). Leuphasyl TFA: Mechanism of Action and Applications.

⚖️ Legal Compliance & Regulatory Information

FOR LABORATORY RESEARCH USE ONLY.
NOT FOR HUMAN OR VETERINARY USE.
NOT FOR COSMETIC USE (IN VIVO).
NOT FOR FOOD OR DRUG USE.

United States Compliance:
This product is sold in strict compliance with the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. § 301 et seq. It is explicitly labeled for “Research Use Only” and is not intended for introduction into food, drugs, or cosmetics intended for consumer use. By purchasing this product, the buyer certifies that they are a qualified scientific professional or are acting under the direct supervision of a qualified professional in a laboratory setting.

DEA Compliance:
Pentapeptide-18 is a synthetic peptide analog of enkephalin. It is NOT a controlled substance under the Controlled Substances Act (21 U.S.C. § 801 et seq.). It has no known abuse liability or opioid analgesic activity at concentrations used in topical/in vitro research. However, buyers should verify compliance with local institutional biosafety committees.

Export Compliance:
Buyer is responsible for compliance with all applicable export control laws and regulations, including the International Traffic in Arms Regulations (ITAR) and Export Administration Regulations (EAR) .

California Prop 65: This product may contain chemicals known to the State of California to cause cancer and/or reproductive toxicity. Handle with appropriate PPE.

⭐ Customer Testimonials (Verified Researchers)

“We needed a reliable source of Pentapeptide-18 for our δ-opioid receptor signaling studies. The COA included chiral HPLC confirmation of D-Ala content—critical for our binding affinity calculations. Most vendors don’t even test for epimerization. Buy Peptides Online USA delivered.”
— Dr. Elena M., Principal Investigator, Neuropharmacology Lab, Stanford University 🏆

“I was using Pentapeptide-18 from a different supplier and getting inconsistent calcium flux inhibition in our DRG neuron cultures. Switched to this source—the MS showed exact mass and the HPLC purity was >99%. My data is finally reproducible.”
— Dr. James W., Research Scientist, Pain Research Group, UCSD 🧪✅

“Fast shipping, excellent communication, and the peptide dissolved instantly in water as specified. The amino acid analysis confirmed correct 1:1:1:1:1 stoichiometry. Will definitely re-order for our ongoing neuromuscular junction research.”
— Dr. Anita V., Associate Professor, Physiology & Biophysics, University of Chicago 🔬

“I appreciated that the product page clearly distinguishes Pentapeptide-18 from Pentapeptide-3. The CAS number verification on the COA gave me confidence I was using the correct molecular entity. This is basic science rigor that many peptide vendors ignore.”
— Michael R., PhD Candidate, Molecular Pharmacology, Harvard Medical School 📊

🛒 How to Buy Pentapeptide-18 Online USA

Step 1: Select your quantity from the dropdown (100 mg, 250 mg, 500 mg, or 1 g).
Step 2: Click ADD TO CART.
Step 3: Checkout securely via Stripe (credit card) or select cryptocurrency for instant discount.
Step 4: Receive order confirmation with tracking number within 1 hour.
Step 5: Download your lot-specific COA from your account dashboard immediately upon shipment.

Bulk/Wholesale Orders (≥5 grams):

• Custom synthesis available for GMP-grade material (non-GMP research grade standard)
• Multi-gram pricing discounts available
• Standing purchase agreements (SPAs) for institutional buyers
• Contact: b2b@buypeptidesonlineusa.com

🔬 Summary: Why This Molecule Matters

Pentapeptide-18 represents a landmark achievement in biomimetic peptide engineering. By taking the structure of an endogenous human neuropeptide (enkephalin) and introducing a single strategic D-amino acid substitution, medicinal chemists created a molecule with:

• ✅ Enhanced proteolytic stability (D-Ala vs. Gly)
• ✅ Preserved receptor binding affinity (δ-opioid receptor agonism)
• ✅ Reduced oxidation risk (Leu vs. Met)
• ✅ Excellent aqueous solubility (no acylation required)

This is rational drug design—applied to research biochemistry.

When you purchase Pentapeptide-18 from Buy Peptides Online USA, you are not buying a “cosmetic ingredient.” You are acquiring a precisely characterized chemical tool for investigating GPCR signaling, synaptic transmission, and neuromodulation.

We supply the reagent. You drive the discovery. 🔬🧠⚡

⚠️ FINAL VERIFICATION WARNING:

Pentapeptide-18 (Leuphasyl®; CAS 64963-01-5; MW 569.65; Sequence Tyr-D-Ala-Gly-Phe-Leu-OH) is NOT the same as:

• Pentapeptide-3 (Vialox®; CAS ~135679-88-8; Sequence Gly-Pro-Arg-Ile-Ala-OH)
• Acetyl Hexapeptide-3 (Argireline®; CAS 616204-22-9)
• Pal-GHK (CAS 147732-56-7)
• Pal-AHK (CAS 849061-97-6)
• Any “Copper Peptide”

These sequences and mechanisms are NOT interchangeable. Verify your CAS number against the COA immediately upon receipt. Buy Peptides Online USA is not responsible for experimental failure due to sequence misidentification.