Palmitoyl Pentapeptide-4 is a synthetic, lipopeptide derivative of a specific sequence found in the C-terminal region of human type I procollagen. This region is known to play a role in the processing and assembly of collagen fibers. The peptide was designed to mimic this endogenous signaling sequence, with the addition of a palmitoyl fatty acid chain to enhance its skin penetration and stability. Its discovery and development were driven by research into wound healing and skin aging, specifically targeting the mechanisms of collagen synthesis and extracellular matrix (ECM) remodeling. Its significance lies in its application as a model compound in dermatological research, particularly for studying the stimulation of collagen, fibronectin, and glycosaminoglycan production in dermal fibroblasts, making it a prominent subject in cosmetic and skin repair science.
Quick Facts
| Also Known As | Pal-KTTKS, Palmitoyl Oligopeptide, Matrixyl, Pentapeptide-4 |
|---|---|
| Sequence | Lys-Thr-Thr-Lys-Ser (KTTKS) |
| Molecular Formula | C39H75N7O10 |
| Molecular Weight | 802.1 Da |
| PubChem CID | 9897237 |
Research Parameters
| Half-Life | Unknown for systemic administration. Topically applied, its activity is localized with no established pharmacokinetic half-life. |
|---|---|
| Stability | Lyophilized powder is stable for at least 24 months when stored at -20°C, protected from light and moisture. After reconstitution in a suitable solvent (e.g., sterile water or buffer), it should be aliquoted and stored at -20°C or below for long-term stability; stability after reconstitution is typically several weeks when handled aseptically and kept frozen. |
| Solubility | Soluble in sterile water, bacteriostatic water, or phosphate-buffered saline (PBS). The palmitoyl moiety may require brief sonication or gentle warming for complete dissolution. |
| Vial Size | 10 mg |
| Storage (Lyophilized) | -20°C or below, protected from light and moisture. Desiccated storage is recommended. |
| Storage (Reconstituted) | -20°C or below in aliquots to avoid repeated freeze-thaw cycles. For short-term use, may be stored at 2-8°C for up to 7 days. |
| Typical Research Dose | Not applicable for systemic dosing. In topical research formulations, typical concentration is 3-10 ppm (µg/mL or mg/L). |
| Cycle Parameters | Research protocols for topical application typically involve daily application for continuous periods of 4 to 12 weeks, with no established "on/off" cycle. |
| Amino Acid Count | 5 |
Mechanism of Action
Palmitoyl Pentapeptide-4 is believed to function primarily as a signal peptide that stimulates key components of the extracellular matrix in dermal fibroblasts. The proposed mechanism involves the peptide acting on fibroblast cell membranes to promote the synthesis of structural proteins and other matrix components.
Fibroblast Activation via Integrin Signaling: The peptide sequence (KTTKS) may interact with or mimic ligands for integrin receptors on dermal fibroblasts. This interaction is thought to initiate intracellular signaling cascades, such as the MAPK/ERK pathway, leading to increased gene expression of collagen and other ECM proteins.
Increased Collagen I and III Production: Research indicates the peptide upregulates the transcription of genes encoding for type I and type III collagen. This is mediated through the activation of transcription factors like SMAD, which are downstream of TGF-β signaling pathways, a key regulator of collagen synthesis.
Stimulation of Fibronectin and Glycosaminoglycans: Beyond collagen, the peptide has been shown to increase the production of fibronectin, a glycoprotein crucial for cell adhesion and migration, and glycosaminoglycans (GAGs) like hyaluronic acid, which contribute to skin hydration and volume.
Anti-Collagenase Activity: Some studies suggest Palmitoyl Pentapeptide-4 may help protect existing collagen by inhibiting matrix metalloproteinases (MMPs), specifically collagenase (MMP-1), thereby reducing collagen degradation in the skin.
Research Applications
Dermatological and Wound Healing Research: In vitro and ex vivo studies using human dermal fibroblasts and skin models have demonstrated that Palmitoyl Pentapeptide-4 can stimulate the production of collagen types I and III, fibronectin, and hyaluronic acid. This makes it a valuable research tool for investigating mechanisms of skin aging, photoaging, and wound repair. Research focuses on its potential to improve skin elasticity, reduce the appearance of wrinkles, and enhance the overall structure of the dermal extracellular matrix.
Cosmetic Science and Formulation: The peptide is extensively studied in the context of topical delivery systems. Research investigates its stability in formulations, skin penetration efficacy (enhanced by the palmitoyl moiety), and its synergistic effects with other active ingredients like retinoids, vitamin C, and other peptides. Studies often measure clinical parameters such as skin roughness, elasticity, and density using techniques like ultrasound and profilometry.
Safety & Side Effects
Based on available research, primarily from topical application studies, Palmitoyl Pentapeptide-4 has shown a favorable safety profile. In clinical trials involving topical formulations, it has been generally well-tolerated with minimal reports of adverse effects. Anecdotally, in the context of cosmetic use, side effects are rare but could theoretically include mild, transient local skin reactions such as redness, itching, or irritation, particularly in individuals with sensitive skin. There is no data on systemic toxicity from topical application, and its safety for oral or injectable use has not been established. Theoretical concerns are minimal due to its peptide nature and localized application.
Dosage Information
This information is derived from published in vitro, ex vivo, and limited clinical research studies only. It is not intended for human therapeutic use. Typical research doses in cell culture studies range from 1 to 50 µM. In the few reported human topical clinical trials, formulations contained the peptide at concentrations between 3 to 10 ppm (parts per million). Administration in research is exclusively topical, applied once or twice daily. Study durations in clinical research have typically ranged from 4 weeks to 3 months.
References
Lintner, K., & Peschard, O. (2000). Biologically active peptides: from a laboratory bench curiosity to a functional skin care product. International Journal of Cosmetic Science, 22(3), 207-218.nnRobinson, L. R., Fitzgerald, N. C., Doughty, D. G., Dawes, N. C., Berge, C. A., & Bissett, D. L. (2005). Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. International Journal of Cosmetic Science, 27(3), 155-160.nnZhang, L., & Falla, T. J. (2009). Cosmeceuticals and peptides. Clinics in Dermatology, 27(5), 485-494.nnFields, K., Falla, T. J., Rodan, K., & Bush, L. (2009). Bioactive peptides: signaling the future. Journal of Cosmetic Dermatology, 8(1), 8-13.nnGorouhi, F., & Maibach, H. I. (2009). Role of topical peptides in preventing or treating aged skin. International Journal of Cosmetic Science, 31(5), 327-345.nnSchagen, S. K. (2017). Topical peptide treatments with effective anti-aging results. Cosmetics, 4(2), 16.