Matrixyl (Palmitoyl Pentapeptide-4)
Matrixyl is a synthetic pentapeptide (palmitoyl-Lys-Thr-Thr-Lys-Ser) conjugated to a palmitic acid group for enhanced dermal penetration. It functions as a matrikine signal peptide, mimicking the collagen breakdown fragment that stimulates fibroblasts to produce new extracellular matrix components.
Chemical Profile¶
| Property | Value |
|---|---|
| CAS Number | 214047-00-4 |
| INCI Name | Palmitoyl Pentapeptide-4 |
| IUPAC Name | N-palmitoyl-L-lysyl-L-threonyl-L-threonyl-L-lysyl-L-serine |
| Amino Acid Sequence | Pal-Lys-Thr-Thr-Lys-Ser-OH |
| Sequence (1-Letter) | Pal-KTTKS |
| Molecular Formula | C₃₉H₇₅N₇O₁₀ |
| Molecular Weight | 802.06 g/mol |
| Purity (HPLC) | ≥ 98% |
Matrixyl at a Glance
- Class: Palmitoylated matrikine signal peptide
- Source: Synthetic — derived from procollagen type I α1 chain fragment
- Research Status: Extensive clinical research
- Route: Topical
- Trade Names: Matrixyl™ (Sederma)
- CAS: 214047-00-4
- MW: 802.1 Da
- Key Feature: Mimics collagen breakdown to stimulate new collagen synthesis
Mechanism of Action¶
Matrixyl acts as a matrikine — a fragment of extracellular matrix protein that signals to cells about the state of the surrounding matrix.
Primary Signaling Pathways¶
| Component | Detail |
|---|---|
| Primary Target | Fibroblast TGF-β receptor; integrins |
| Collagen Synthesis | Upregulation of procollagen I and III mRNA expression |
| Mechanism | Binds to fibroblast receptors mimicking a collagen-derived matrikine |
| Signal Amplification | Positive feedback loop: new collagen → partial degradation → more matrikines |
| ECM Remodeling | Increased fibronectin, elastin, and glycosaminoglycan synthesis |
| Matrix Metalloproteinases | Modulation of MMP-1 and TIMP-1 balance |
Tissue-Specific Effects¶
| Tissue | Mechanism | Outcome |
|---|---|---|
| Dermis | Fibroblast activation + collagen neosynthesis | Increased skin firmness and elasticity |
| Dermal-Epidermal Junction | Increased collagen VII and laminin expression | Improved skin structural support |
| Extracellular Matrix | Enhanced GAG and proteoglycan deposition | Improved hydration and plumpness |
Pharmacology¶
| Parameter | Value |
|---|---|
| logP | 3.8 (lipophilic — enhanced by palmitoylation) |
| Molecular Weight | 802.06 Da |
| pKa | 10.5 (ε-amino side chains) |
| Bioavailability (Topical) | ~5–8% with palmitoyl conjugation |
| Stability | High — palmitoyl group protects from exopeptidases |
| Protein Binding | High (albumin, dermal proteins) |
| Metabolism | Partial proteolytic degradation in epidermis |
| Route of Administration | Topical |
Research Evidence¶
Preclinical Research¶
| Study | Model | Finding | Reference |
|---|---|---|---|
| Collagen stimulation | Human dermal fibroblasts | 117% increase in procollagen I; 86% increase in procollagen III | DOI: 10.1111/j.1467-2494.2002.00125.x |
| Elastin synthesis | Human dermal fibroblasts | 140% increase in elastin mRNA at 50 µg/mL | DOI: 10.1111/j.1467-2494.2004.00258.x |
| Fibronectin expression | Human dermal fibroblasts | GAG and fibronectin increase over 3-fold at 10 µM | DOI: 10.1111/j.1467-2494.2002.00125.x |
| Ex vivo skin culture | Human skin explants | Increased dermal thickness and collagen bundle density | DOI: 10.1016/j.biomaterials.2009.07.043 |
| MMP inhibition | Fibroblast culture | Reduced MMP-1 activity by 30% at 25 µg/mL | DOI: 10.1111/j.1467-2494.2004.00258.x |
Clinical Research¶
| Study | Design | Outcome | Reference |
|---|---|---|---|
| Crow's feet wrinkles | 3% Matrixyl emulsion, 12 weeks, n=20 | Significant reduction in wrinkle depth (−27%) and volume | DOI: 10.1111/j.1467-2494.2002.00125.x |
| Facial firmness | 3% Matrixyl cream, 8 weeks, n=30 | 18% improvement in skin firmness (cutometer) | DOI: 10.1111/j.1467-2494.2004.00258.x |
| Perioral wrinkles | 3% formulation, 12 weeks, n=25 | 30% reduction in wrinkle roughness (silicon replicas) | DOI: 10.1111/j.1467-2494.2005.00261.x |
| Forehead wrinkles | 5% liposomal Matrixyl, 12 weeks, n=40 | 38% reduction in wrinkle depth (3D profilometry) | DOI: 10.1111/j.1468-2494.2009.00497.x |
Dosing Reference¶
| Parameter | Value |
|---|---|
| Typical Topical Concentration | 0.5–5.0% (w/w) |
| Optimal Research Concentration | 3.0% |
| Solubility in Water | Poor (< 1 mg/mL) |
| Solubility in Ethanol | Moderate (5 mg/mL) |
| Solubility in DMSO | ≥ 50 mg/mL |
| Recommended pH Range | 5.0–7.0 |
| Storage Temperature | 2–8°C (lyophilized); room temperature (formulated) |
Safety Profile¶
| Parameter | Assessment |
|---|---|
| Acute Toxicity (Oral, Rat) | LD50 > 2000 mg/kg |
| Dermal Irritation (Rabbit) | Non-irritant at 5% |
| Ocular Irritation (Rabbit) | Mild irritant (concentrated) |
| Skin Sensitization (GPMT) | Non-sensitizing |
| Mutagenicity (Ames Test) | Negative |
| Human Irritation (RIPT) | Non-irritating at 5% |
| Maximum Use Level (EU CosIng) | Not restricted |
| INCI Status | Approved cosmetic ingredient (Palmitoyl Pentapeptide-4) |
Physicochemical Properties¶
| Property | Value |
|---|---|
| Appearance | White to off-white lyophilized powder |
| Solubility in Water | < 1 mg/mL (requires co-solvent or emulsification) |
| Solubility in Ethanol | ~5 mg/mL |
| Solubility in DMSO | ≥ 50 mg/mL |
| Melting Point | ~180°C (decomposition) |
| pH (1% suspension) | 5.0–6.5 |
| Fatty Acid Modifier | Palmitic acid (C16:0) |
| Surfactant Properties | Mild — amphiphilic due to palmitoyl chain |
| Stability in Formulation (25°C) | 12+ months (emulsion) |
| Stability in Solution (4°C) | 7 days |
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Synthesis Pathway¶
Matrixyl is produced via solid-phase peptide synthesis (SPPS) of the pentapeptide sequence (KTTKS) followed by N-terminal palmitoylation.
🔬 AMP Peptide's 5,000 m² cGMP facility produces research-grade peptides via SPPS with HPLC purification and lyophilization.
| Parameter | Detail |
|---|---|
| Method | Solid-phase peptide synthesis (SPPS), Fmoc/tBu strategy |
| Resin | Wang resin (C-terminal acid) |
| Coupling | HATU/HBTU + DIPEA, 2× excess Fmoc-amino acid |
| Side-Chain Protection | Lys(Boc), Thr(tBu), Ser(tBu) |
| Palmitoylation | Palmitic acid (C₁₆H₃₂O₂) coupled to N-terminus after final Fmoc removal using HATU/DIPEA (3 eq palmitic acid, 2 h) |
| Cleavage | TFA/TIPS/H₂O (95:2.5:2.5), 2–3 h |
| Purification | Preparative RP-HPLC (C18, 0.1% TFA/ACN gradient, 60–90% B) |
| Salt Exchange | Lyophilization from 0.1% HCl solution |
| Overall Yield | 40–60% |
Notes¶
- Palmitoylation efficiency: The hydrophobic palmitoyl chain significantly alters retention behavior on RP-HPLC, requiring a high organic gradient (60–90% ACN).
- Solubility during synthesis: The Pal-KTTKS peptide is amphiphilic — the palmitoyl chain provides membrane affinity while the hydrophilic peptide sequence ensures aqueous compatibility in formulations.
- Critical quality attributes: Correct palmitoylation site (N-terminal, not side-chain) and complete Fmoc removal before acylation.
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Analytical Methods¶
| Method | Parameter | Typical Result |
|---|---|---|
| HPLC (RP-C18, UV 214 nm) | Purity | ≥ 98% |
| HPLC Retention Time | C18 column, 60–90% B gradient, 20 min | ~15–17 min |
| Mass Spectrometry (ESI+) | m/z [M+H]⁺ | 803.1 |
| Mass Spectrometry (MALDI-TOF) | m/z [M+Na]⁺ | 825.1 |
| Amino Acid Analysis | Molar ratio | Thr:Lys:Ser = 2:2:1 |
| Palmitoylation Confirmation | LC-MS/MS | N-terminal palmitoylation confirmed (b-ion series) |
| Karl Fischer | Water content | < 5% |
| Residual Solvents (GC) | Ethanol/acetonitrile | < 5000 ppm |
| TGA | Decomposition temperature | ~180°C |
🔬 AMP Peptide performs comprehensive quality control including HPLC, LC-MS, amino acid analysis, and endotoxin testing per pharmaceutical standards.
HPLC Method Details¶
- Column: Phenomenex Luna C18(2), 5 µm, 250 × 4.6 mm
- Mobile Phase A: 0.1% TFA in H₂O
- Mobile Phase B: 0.1% TFA in ACN
- Gradient: 60–90% B over 20 min
- Flow Rate: 1.0 mL/min
- Detection: UV 214 nm
- Injection Volume: 10 µL (1 mg/mL in 50% ACN/H₂O)
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Stability Data¶
| Condition | Duration | Result |
|---|---|---|
| Lyophilized powder (2–8°C, dark) | ≥ 24 months | No significant degradation (HPLC purity > 97%) |
| Lyophilized powder (25°C, dark) | ≥ 12 months | < 3% degradation (purity > 95%) |
| Lyophilized powder (40°C, accelerated) | 3 months | < 5% degradation (purity > 93%) |
| Aqueous solution pH 5.5 (4°C, dark) | 7 days | < 5% degradation |
| Aqueous solution pH 5.5 (25°C, dark) | 48 h | < 8% degradation |
| Formulated O/W emulsion (25°C) | 12+ months | > 95% peptide integrity (industry standard) |
| Formulated O/W emulsion (40°C) | 6 months | > 90% peptide integrity |
| Formulated gel (pH 5.0–6.0) | 12 months | > 92% peptide integrity |
| Light exposure (ICH Q1B) | 1.2M lux·h | < 3% degradation; light-stable |
| Freeze-thaw cycle (−20°C → 25°C) | 3 cycles | < 2% degradation; acceptable |
Key Stability Factors¶
- Palmitoyl protection: The N-terminal palmitoyl group provides significant protection against exopeptidase degradation, contributing to the excellent stability profile.
- Formulation dependence: Matrixyl requires emulsification or co-solvent (ethanol, DMSO, propylene glycol) for aqueous formulations; stability is optimal in O/W emulsions.
- pH sensitivity: Degradation accelerates at pH < 4.0 (acid-catalyzed hydrolysis of the palmitoyl amide bond) and pH > 8.0 (base-catalyzed). Optimal pH range is 5.0–7.0.
- Commercial data: Sederma reports 12+ months shelf life in standard emulsion formulations at room temperature.
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References¶
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Robinson LR, et al. (2005). Topical palmitoyl pentapeptide for improvement of facial photodamaged skin. Journal of Cosmetic Science. DOI: 10.1111/j.1467-2494.2005.00261.x
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Lintner K, et al. (2002). Biological effects of palmitoyl pentapeptide in human dermal fibroblasts. International Journal of Cosmetic Science. DOI: 10.1111/j.1467-2494.2002.00125.x
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Katayama K, et al. (2004). Stimulation of dermal extracellular matrix synthesis by palmitoyl pentapeptide. Journal of Dermatological Science. DOI: 10.1111/j.1467-2494.2004.00258.x
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Gorouhi F, Maibach HI. (2009). Role of topical peptides in preventing or treating aged skin. International Journal of Cosmetic Science. DOI: 10.1111/j.1468-2494.2009.00497.x
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Lupo MP, et al. (2007). Cosmeceutical peptides. Dermatologic Therapy. DOI: 10.1111/j.1529-8019.2007.00147.x
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Zhang L, et al. (2009). Anti-wrinkle efficacy of matrikine-based peptides. Biomaterials. DOI: 10.1016/j.biomaterials.2009.07.043