Palmitoyl Tetrapeptide-7 (Pal-GQPR)

Synthetic Peptides in Cosmetic Products

Synthetic peptides function as peptide ligands that act on the cellular receptors to modulate the function of cells. Synthetic peptides present in cosmetic products weigh less than 500 Da and penetrate through the stratum corneum of the skin to exert beneficial effects. Chemical modifications are employed to enhance the penetrability of synthetic peptides. These substances are categorized as signal peptides, carrier peptides, neurotransmitter inhibitory peptides, and enzyme inhibitory peptides. Palmitoyl tetrapeptide-7 or Pal-GQPR is a signal peptide that is used in cosmetic products for various dermatologic benefits. (Resende et al., 2021)

  1. Common Dermatologic Conditions

Following are the common dermatologic conditions that are characterized by inflammation and oxidative reactions of the skin. 

  • Psoriasis

This is a chronic inflammation of the skin and it is characterized by the proliferation of the dermis and infiltration of the skin layers with inflammatory immune cells. The inflammatory mediators commonly involved in the pathogenesis of psoriasis include IL-17, IL-23, and tumor necrosis factor (TNF). These inflammatory mediators are involved in the occurrence of inflammatory cutaneous lesions. The inflammatory mediators mediate the production and secretion of chemokines, cytokines, and antimicrobial peptides by the epidermal keratinocytes. (Sawada et al., 2021)

  • Eczema

Eczema, also termed atopic dermatitis, is a dermatologic condition characterized by genetic mutations encoding filaggrin. This protein plays a significant role in maintaining the skin barrier function found in the stratum corneum, which also aids in the retention of natural skin moisture. Genetic mutations of filaggrin lead to the production and secretion of proinflammatory cytokines and disruption of the skin barrier. (Sawada et al., 2021)

  • Contact Dermatitis 

Contact dermatitis is a dermatologic condition caused by exposure to several etiological factors. These factors include metal ions, toxic chemicals, and reactive chemicals. The two forms of stimulating agents are contact irritants and contact allergens. While contact irritants cause T-cell response, the contact allergens elicit innate and adaptive immune responses. In response to these chemical agents, the keratinocytes produce proinflammatory cytokines responsible for the characteristic presentation of contact dermatitis. The chemical agents cause alterations in the dermis, disrupt the normal skin barrier, and stimulate the release of cytokines. The allergic form of contact dermatitis is associated with repeated exposure of skin to haptens. (Litchman et al., 2022) 

  • Dermal Aging 

Aging or senescence is an inevitable physiologic process encompassing age-related alterations in different body tissues including skin. Dermal aging is marked by the appearance of fine lines and wrinkles along with a loss of elasticity of the skin. Dermal aging involves impairment of the function of fibroblasts which then leads to a reduction of the levels of collagen in the extracellular matrix of the dermis. Under normal circumstances, the regulatory proteins modulate the balance between apoptosis and maturation. Dermal aging is characterized by the impaired function of regulatory proteins which disrupt the balance between these two mechanisms. Impaired repair mechanisms cause the cellular changes to accumulate and disrupt the normal cellular physiology. The aging process affects elastic fibers, glycosaminoglycans, and proteoglycans present in the extracellular matrix. Dermal aging involves the enhanced activity of matrix metalloproteinases that increase the degradation of proteins in the dermal extracellular matrix. The visible signs of aging are wrinkles, fine lines, and reduced elasticity. (Flint & Tadi, 2020; Shin et al., 2019)

  1. Palmitoyl Tetrapeptide-7
  • Composition

Palmitoyl tetrapeptide-7 or Pal-GQPR is an immunoglobulin G segment with a sequence of N-glycyl-L-glutaminyl-L-prolyl-L-arginine. Palmitoyl tetrapeptide-7 suppresses the secretion of IL-6 which functions to reduce inflammation following exposure to ultraviolet B radiation. Palmitoyl tetrapeptide-7 also stimulates the production of collagen VII and laminin IV and V, making this peptide an essential constituent of anti-aging cosmetic products. (Resende et al., 2021)

  • Synthesis of Palmitoyl Tetrapeptide-7

Palmitoyl tetrapeptide-7 is synthesized using two distinct solid-phase methodologies. The first methodology involves the attachment of amino acid with H-Arg-HMPB-ChemMatrix resin. This is followed by resin wash and Smoc deprotection with the subsequent coupling of another amino acid with the compound, Smoc-glutamine, and Smoc-glycine. After achieving the desired peptide molecule, the peptide is subjected to palmitoylation and cleavage from the resin. Palmitoyl tetrapeptide-7 is formed after precipitation and lyophilization of the peptide. (Knauer et al., 2020)

The second methodology of palmitoyl tetrapeptide-7 synthesis is marked by the addition of a soluble fragment that enhances the water solubility of this synthetic peptide. Five hydrophilic lysines are coupled with the amino acid resin, followed by the introduction of connecting arm of p-hydroxybenzoic acid and coupling of the remaining amino acids with peptide sequence, Pal-Gly-Gln-Pro-Arg-OH. The resulting molecule is then subjected to the elimination of Fmoc protecting groups, cleavage of resin, purification, and hydrolysis of the refined peptide to yield palmitoyl tetrapeptide-7. (Kleid et al., 1985)

  • Safety Profile and Toxicity 

The mean irritation index of palmitoyl tetrapeptide-7 for ocular irritation is 3.75. Palmitoyl tetrapeptide-7 produces slight ocular irritation upon topical application of this synthetic peptide. Palmitoyl tetrapeptide-7 does not produce allergic contact sensitization and skin irritation. Studies do not report the developmental and reproductive toxicity of palmitoyl tetrapeptide-7. Similarly, the studies do not report carcinogenic effects of palmitoyl tetrapeptide-7. The genotoxicity of palmitoyl tetrapeptide-7 is evaluated using the Ames test. The test concludes that this synthetic peptide is nonmutagenic and does not have genotoxic effects. (Johnson et al., 2018)

  1. Cosmetic Benefits of Palmitoyl Tetrapeptide-7
  • Wrinkle Improvement 

The topical application of palmitoyl tetrapeptide-7 improves facial wrinkles as the synthetic peptide promotes the production of collagen and other extracellular proteins. (Hahn et al., 2016)

  • Photoaging Repair Effects 

The anti-aging properties against photoaging of palmitoyl tetrapeptide-7 are attributed to the restoration of normal levels of fibrillin-1 which is an important constituent of fibrillin-rich microfibrils. The synthetic peptide also improves the skin texture. At the onset of aging, fibrillin-1, which is an important glycoprotein constituent of oxytalan fibers of fibrillin-rich microfibrils, tends to reduce in the papillary dermis. Fibrillin-1 also serves as an effective biomarker for the evaluation of photoaging repair properties of cosmetic products. (Watson et al., 2009)

  • Cellulite Reduction 

Cellulite is marked by an orange peel appearance of the skin that arises due to the bulging of underlying fat lobules into the dermis of the skin. Cellulite is commonly seen on thighs, hips, and buttocks and less commonly on the abdomen. Cellulite precipitates the onset of skin aging, particularly in women older than 30 years. Topical application of palmitoyl tetrapeptide-7 on the affected areas tends to improve the skin tonicity, stubborn cellulite, and orange peel appearance of the skin, particularly on hips, buttocks, and thighs. Concomitant massaging of the affected area tends to improve drainage and promotes microcirculation of the involved region. Reduction of cellulite and drainage of the affected regions tend to reduce the visible signs of aging.  (Dupont et al., 2014)



Dupont, E., Journet, M., Oula, M. L., Gomez, J., Léveillé, C., Loing, E., & Bilodeau, D. (2014). An integral topical gel for cellulite reduction: results from a double-blind, randomized, placebo-controlled evaluation of efficacy. Clin Cosmet Investig Dermatol, 7, 73-88. 

Flint, B., & Tadi, P. (2020). Physiology, aging. 

Hahn, H. J., Jung, H. J., Schrammek-Drusios, M. C., Lee, S. N., Kim, J. H., Kwon, S. B., An, I. S., An, S., & Ahn, K. J. (2016). Instrumental evaluation of anti-aging effects of cosmetic formulations containing palmitoyl peptides, Silybum marianum seed oil, vitamin E, and other functional ingredients on aged human skin. Exp Ther Med, 12(2), 1171-1176. 

Johnson, W., Bergfeld, W. F., Belsito, D. V., Hill, R. A., Klaassen, C. D., Liebler, D. C., Marks, J. G., Shank, R. C., Slaga, T. J., Snyder, P. W., Gill, L. J., & Heldreth, B. (2018). Safety Assessment of Tripeptide-1, Hexapeptide-12, Their Metal Salts and Fatty Acyl Derivatives, and Palmitoyl Tetrapeptide-7 as Used in Cosmetics. International Journal of Toxicology, 37(3_suppl), 90S-102S. 

Kleid, D. G., Yansura, D. G., Heyneker, H. L., & Miozzari, G. F. (1985). The production method of a polypeptide product. In: Google Patents.

Knauer, S., Koch, N., Uth, C., Meusinger, R., Avrutina, O., & Kolmar, H. (2020). Sustainable Peptide Synthesis Enabled by a Transient Protecting Group. Angewandte Chemie International Edition, 59(31), 12984-12990. 

Litchman, G., Nair, P. A., Atwater, A. R., & Bhutta, B. S. (2022). Contact Dermatitis. In StatPearls. StatPearls Publishing

Copyright © 2022, StatPearls Publishing LLC. 

Resende, D., Ferreira, M. S., Sousa-Lobo, J. M., Sousa, E., & Almeida, I. F. (2021). Usage of Synthetic Peptides in Cosmetics for Sensitive Skin. Pharmaceuticals (Basel), 14(8). 

Sawada, Y., Saito-Sasaki, N., Mashima, E., & Nakamura, M. (2021). Daily Lifestyle and Inflammatory Skin Diseases. Int J Mol Sci, 22(10). 

Shin, J. W., Kwon, S. H., Choi, J. Y., Na, J. I., Huh, C. H., Choi, H. R., & Park, K. C. (2019). Molecular Mechanisms of Dermal Aging and Antiaging Approaches. Int J Mol Sci, 20(9). 

Watson, R. E., Ogden, S., Cotterell, L. F., Bowden, J. J., Bastrilles, J. Y., Long, S. P., & Griffiths, C. E. (2009). Effects of a cosmetic ‘anti-aging’ product improve photoaged skin [corrected]. Br J Dermatol, 161(2), 419-426. 

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