Palmitoyl Tripeptide-5 (Palmitoyl Tripeptide-3, Pal-KVK, Syn-COLL)

Synthetic Peptides in Cosmetic Products

Synthetic peptides offer a wide range of benefits for the skin. They function as peptide ligands that may stimulate or inhibit cell receptors and regulate cellular function. Peptides in cosmetic products weigh less than 500 Da with moderate penetrability through the stratum corneum. Additionally, the chemical modifications of peptides enhance the penetrability of these substances.

 Peptides found in cosmetic products are classified as signal peptides, inhibitory enzyme peptides, carrier peptides, and neurotransmitter-inhibitory peptides. Palmitoyl tripeptide-5 is a synthetic signal peptide found in cosmetic products that has numerous skin benefits, particularly for those who have sensitive skin types. (Resende et al., 2021)

Skin condition’s onset of inflammation in the skin is an adaptive measure to external environmental stimuli. Internal physiological factors also influence the severity of skin inflammation. Subsequent sections describe the pathogenesis of different inflammatory skin conditions. (Sawada et al., 2021)

  1. Psoriasis 

Psoriasis is characterized by chronic inflammation of the skin. This condition involves infiltration of skin layers with inflammatory immune cells and epidermal proliferation. The tumor necrosis factor (TNF) mediates the interleukins IL-23 and IL-17. These inflammatory mediators play an essential role in the pathogenesis of psoriasis and the onset of inflammatory skin lesions. IL-17 promotes epidermal inflammatory reactions. This also stimulates the keratinocytes to synthesize and release antimicrobial peptides, inflammatory cytokines, and chemokines. (Sawada et al., 2021)

  1. Dermatitis 

Contact dermatitis is characterized by inflammation of the skin. It  arises due to skin contact with toxic chemicals, metal ions, and reactive chemicals. Contact irritants refer to the T cell response, whereas contact allergens refer to an adaptive and innate immune response against responsible agents. The secretion of proinflammatory cytokines causes irritant contact dermatitis by keratinocytes in response to chemical irritants. These chemical irritants lead to disruption of the skin barrier, cellular alterations in the epidermis, and the release of cytokines. Allergic contact dermatitis occurs due to repetitive exposure of skin to haptens. The two phases of contact dermatitis are the sensitization and elicitation phases, characterized by induction of T cells and activation of effector T cells, respectively. (Litchman et al., 2022)

  1. Eczema (Atopic Dermatitis)

Eczema or atopic dermatitis is associated with filaggrin gene mutation. Filaggrin plays an essential role in optimal skin barrier function in the stratum corneum. In the upper part of the stratum corneum, filaggrin releases free amino acids essential for moisturizing the skin. Filaggrin gene mutation leads to disruption of the skin barrier. This leads to the activation of Langerhan cells and keratinocytes. These cells release proinflammatory cytokines, including IL-33, IL-13, IL-4, IL-12, IL-31, and thymic stromal lymphopoietin (TSLP). A higher nickel concentration in the serum is evident in individuals suffering from intrinsic atopic dermatitis or eczema. This leads to the production of IL-8 by fibroblasts. (Sawada et al., 2021) 

  1. Aging

Aging or senescence is a normal physiological process characterized by the loss of bioprotective and degenerative processes over certain duration. Despite being a normal physiological process, aging is associated with a pro-disease state and manifests as widespread derangement of organ functions. Aging is an inevitable process that every human has to encounter at some point. At the cellular level, aging can be described as the function of telomeres. As a person grows older, the telomeres shorten with increasing division cycles. This leads to a reduction in the protection offered by the telomeres, making the cells susceptible to DNA damage. Cellular changes in aging result in the cessation of replicative and metabolic functions of the cells. (Flint & Tadi, 2020) 

Underling aging pathologies include the production of free radicals and reduced regenerative capacity of cells. Under normal circumstances and well-regulated mechanisms, the free radicals are produced in smaller amounts. A higher concentration of free radicals reacts with cellular components. This includes denaturation of proteins, destruction of membrane lipids, destruction of nucleic acids, and damage of cell organelles. The repair mechanisms are overwhelmed by the accumulated cellular damages resulting in the cessation of cellular functions. Apoptosis and maturation of cells are balanced in healthy individuals. Regulatory proteins maintain this balance. The function of regulatory proteins declines with age, with a subsequent decline in the number of healthy and functional cells. (Flint & Tadi, 2020) 

Dermal aging is associated with wrinkles, reduced elasticity, and progressive dermal atrophy. A reduced extracellular matrix causes dermal atrophy. A significant reduction in the collagen content of the extracellular matrix of the dermis is observed. This deteriorates fibroblasts’ function, which leads to a further reduction in the synthesis of collagen. Aging-associated alterations also occur in elastic fibers, proteoglycans, and glycosaminoglycans. This leads to the emergence of reduced elasticity and wrinkles. In aged skin, the levels of matrix metalloproteinase increase. These enzymes are responsible for the degradation of proteins in the extracellular matrix. (Shin et al., 2019) 

Palmitoyl Tripeptide-5

  1. Composition

Palmitoyl tripeptide-5 is a synthetic signal peptide used in cosmetic formulations. The peptide is primarily composed of valine and lysine residues. At the N-terminus of the peptide, a palmitoyl moiety is present. The structural composition of palmitoyl tripeptide-5 mimics the structure of a protein called thrombospondin 1 (TSP-1). Palmitoyl tripeptide-5 can be conjugated with an L-ascorbate moiety at the C-terminus of the synthetic peptide. This conjugated structure is Pal-KVK-AA. Pal-KVK-AA is known for its depigmentation effects on the skin. (Errante et al., 2020; Trookman et al., 2009)

  1. Mechanism of Action 

Palmitoyl tripeptide-5 stimulates the function of transforming growth factor-beta (TGF-β). Activation of TGF-β by palmitoyl tripeptide-5 is similar to that of the TSP-1. This growth factor is responsible for collagen production and suppression of the activity of matrix metalloproteases that degrade collagen. The incorporation of peptide dipalmitoyl hydroxyproline promotes the synthesis of tissue inhibitors of matrix metalloproteases (TIMP), further suppressing collagen degradation. Conjugation of L-ascorbate moiety is responsible for suppressing melanin synthesis, thus, preventing the onset of hyperpigmentation. (Errante et al., 2020; Trookman et al., 2009)

  1. Collagen Biosynthesis and Wound Healing

Stimulation of TGF-β plays an essential role in the modulation of wound healing. The short sequence of TSP-1 mimics the amino acid sequence of palmitoyl tripeptide-5. The similarity in composition aids in the activation of TGF-β. TGF-β stimulates the production of type I and type III collagen by the fibroblasts in the dermis. Collagen production plays a significant role in optimal wound healing. Similarly, a rise in collagen production and deposition by dermal fibroblasts leads to concomitant improvement in wound healing. The simultaneous reduction in collagen degradation by matrix metalloprotease also contributes to the increased collagen concentration in the dermal extracellular matrix. (Schagen, 2017)

 Anti-Wrinkle and Anti-Aging Effect

Palmitoyl tripeptide-5 is a synthetic signal peptide with antiaging properties added to associated cosmetic products. Palmitoyl tripeptide-5 reduces the expression and production of matrix metalloproteases and suppresses the synthesis of proinflammatory cytokines. Anti-inflammatory properties of palmitoyl tripeptide-5 are beneficial for inflammatory skin conditions and changes in the skin associated with dermal aging. Another antiaging effect of palmitoyl tripeptide-5 is inhibition of the catalytic activity of tyrosinase, reducing melanin production. This is important for the management and prevention of hyperpigmentation. (Resende et al., 2021)


  1. Palmitoyl Tripeptide-5 for Irritated Skin

Palmitoyl tripeptide-5 reduces the production of proinflammatory cytokines. It also promotes increased capillary permeability and causes vasodilation. Moreover, this synthetic signal peptide also reduces skin redness. This effect is achieved by combining palmitoyl tripeptide-5 with conjugated linolenic acid and spent grain wax. This makes palmitoyl tripeptide 5 an effective ingredient in cosmetics for inflamed and sensitive skin. (Resende et al., 2021)


Errante, F., Ledwoń, P., Latajka, R., Rovero, P., & Papini, A. M. (2020). Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Front Chem, 8, 572923. 

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

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). 

Schagen, S. K. (2017). Topical peptide treatments with effective anti-aging results. Cosmetics, 4(2), 16. 

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). 

Trookman, N. S., Rizer, R. L., Ford, R., Ho, E., & Gotz, V. (2009). Immediate and Long-term Clinical Benefits of a Topical Treatment for Facial Lines and Wrinkles. J Clin Aesthet Dermatol, 2(3), 38-43.

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