Palmitoyl Tripeptide-38
Palmitoyl Tripeptide-38 (MATRIXYL synthe'6) is a synthetic signal peptide developed by Sederma that stimulates production of six major extracellular matrix proteins, researched for its comprehensive anti-aging and skin-restructuring properties.
Palmitoyl Tripeptide-38 is a synthetic lipopeptide developed by Sederma under the trade name MATRIXYL synthe'6. It is a signal peptide designed to stimulate the simultaneous production of six key extracellular matrix (ECM) components: collagen I, collagen III, collagen IV, fibronectin, hyaluronic acid, and laminin-5.
Overview
Palmitoyl Tripeptide-38 represents the third generation of Sederma's Matrixyl peptide family. While the original Matrixyl (palmitoyl pentapeptide-4) stimulates collagen I, collagen IV, and hyaluronic acid, and Matrixyl 3000 (a blend of palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7) targets collagen synthesis and inflammation, MATRIXYL synthe'6 was engineered to activate a broader spectrum of ECM protein production through a single peptide sequence.
The development rationale centers on the observation that youthful skin integrity depends on a coordinated network of structural proteins, not just collagen alone. Laminin-5 anchors the epidermis to the dermis, fibronectin provides cellular adhesion scaffolding, and hyaluronic acid maintains tissue hydration. Age-related decline in any of these components contributes to visible skin deterioration. By targeting all six simultaneously, Palmitoyl Tripeptide-38 aims to provide more comprehensive skin matrix restoration than peptides addressing individual proteins.
Clinical studies conducted by Sederma demonstrated measurable improvements in wrinkle depth and skin firmness after topical application of formulations containing Palmitoyl Tripeptide-38. The peptide is typically used at concentrations of 2-4 ppm in finished cosmetic products.
Mechanism of Action
Palmitoyl Tripeptide-38 functions as a matrikine -- a bioactive peptide fragment that mimics extracellular matrix degradation products to signal fibroblasts and keratinocytes. Unlike peptides that directly provide structural building blocks, signal peptides like Palmitoyl Tripeptide-38 activate cellular receptors that upregulate endogenous protein synthesis pathways.
The peptide engages growth factor receptors on dermal fibroblasts, triggering intracellular signaling cascades that increase transcription of genes encoding collagen I, III, and IV, fibronectin, hyaluronic acid synthase, and laminin-5 subunits. The palmitoyl (C16 fatty acid) modification enhances lipophilicity, facilitating penetration through the lipid-rich stratum corneum to reach the dermal fibroblast layer.
The simultaneous upregulation of six matrix components mimics the coordinated ECM synthesis observed in young skin, where these proteins are produced in balanced ratios. This coordinated stimulation is hypothesized to produce more physiologically relevant matrix remodeling than single-target approaches.
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Research
Six-Protein Matrix Stimulation
In vitro studies on human dermal fibroblasts demonstrated that Palmitoyl Tripeptide-38 significantly increases synthesis of all six target proteins compared to untreated controls. Collagen I and III synthesis showed dose-dependent increases, while laminin-5 production -- critical for dermal-epidermal junction integrity -- was notably upregulated. This multi-target activity was confirmed by immunoassay and gene expression analysis.
Clinical Anti-Wrinkle Efficacy
Sederma-sponsored clinical trials evaluated Palmitoyl Tripeptide-38 in a cream formulation applied twice daily for 56 days. Silicon replica profilometry showed significant reduction in wrinkle depth and volume, with improvements in skin roughness parameters. Participants reported improvements in skin firmness, smoothness, and overall appearance. The peptide performed comparably to retinol-containing formulations in some parameters without the associated irritation.
Comparison to Earlier Matrixyl Variants
Compared to the original Matrixyl (Pal-KTTKS), which stimulates three ECM proteins, Palmitoyl Tripeptide-38 extends activity to six targets. Compared to Matrixyl 3000, which requires two peptides (palmitoyl tripeptide-1 and palmitoyl tetrapeptide-7) and combines matrix stimulation with anti-inflammatory activity, MATRIXYL synthe'6 achieves broader matrix coverage with a single compound, simplifying formulation.
Safety Profile
Palmitoyl Tripeptide-38 has an excellent safety profile consistent with topical cosmetic peptides. Dermatological testing shows no significant irritation, sensitization, or phototoxicity at recommended use concentrations. The peptide is non-comedogenic and compatible with sensitive skin formulations. Systemic absorption is negligible due to topical application and the relatively large molecular size. No adverse effects have been reported in clinical studies. The ingredient is approved for cosmetic use and included in the International Nomenclature of Cosmetic Ingredients (INCI) database.
Pharmacokinetic Profile
- Half-life
- Not established
Quick Start
- Route
- Topical
Molecular Structure
- Formula
- C₂₈H₅₃N₅O₆ (approximate)
- Weight
- 676.0 Da
- CAS
- 1447824-23-8
- PubChem CID
- 71587932
- Exact Mass
- 675.4605 Da
- LogP
- 3
- TPSA
- 219 Ų
- H-Bond Donors
- 6
- H-Bond Acceptors
- 9
- Rotatable Bonds
- 31
- Complexity
- 943
Identifiers (SMILES, InChI)
InChI=1S/C33H65N5O7S/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-22-30(39)36-27(20-16-18-24-34)31(40)37-28(23-26-46(2,44)45)32(41)38-29(33(42)43)21-17-19-25-35/h27-29H,3-26,34-35H2,1-2H3,(H,36,39)(H,37,40)(H,38,41)(H,42,43)/t27-,28-,29-/m0/s1
RGXYBFJDNNODFP-AWCRTANDSA-NResearch Protocols
topical
Clinical studies conducted by Sederma demonstrated measurable improvements in wrinkle depth and skin firmness after topical application of formulations containing Palmitoyl Tripeptide-38. Safety Profile Palmitoyl Tripeptide-38 has an excellent safety profile consistent with topical cosmetic peptide
| Goal | Dose | Frequency | Duration |
|---|---|---|---|
| General Research Protocol | See literature | Twice daily | 56 days(Route: Topical) |
Quality Indicators
What to look for
- Human clinical trials conducted
Frequently Asked Questions
References (6)
- [6]Gorouhi F, Maibach HI Role of topical peptides in preventing or treating aged skin Int J Cosmet Sci (2009)
- [5]
- [7]Negari et al -- Peptide-based cosmeceuticals: an evolving field of investigation Int J Mol Sci (2023)
- [8]
- [2]
- [1]Lintner K et al Cosmetic peptides Int J Cosmet Sci (2009)
Palmitoyl Tripeptide-1 (Pal-GHK)
Palmitoyl Tripeptide-1 is a lipopeptide fragment of collagen that stimulates collagen I, III, and fibronectin synthesis through TGF-β pathway activation. It is a key component of the Matrixyl 3000 complex.
Palmitoyl Tripeptide-5 (SYN-COLL)
Palmitoyl Tripeptide-5 is a thrombospondin-1 mimetic lipopeptide that activates TGF-β signaling to stimulate procollagen I synthesis, marketed under the SYN-COLL brand name by DSM.