Palmitoyl pentapeptide-4


An overview of Palmitoyl pentapeptide-4 

The potential of topical peptides to improve aging skin has been widely discussed in the cosmetic industry. A peptide that is of particular interest is KTTKS, which is a fragment of pro-collagen I. Palmitoyl Pentapeptide-4(palmitoyl-lysine-threonine-threonine- lysine -serine, Pal KTTKS) is a procollagen pentapeptide fragment that stimulates the production of collagen I, III and fibronectin by fibroblasts in vitro and it has been shown to decrease skin roughness and wrinkles and fine lines after 4 months of application. This pentapeptide has been shown to stimulate the production of dermal matrix in fibroblast culture. As damage to dermal matrix components(e.g.collagen) is associated with skin wrinkling, and increased collagen production(e.g. in phenol peel treatment of skin) is associated with reduction in wrinkles, the topical use of a small molecule will increase the collagen and improve wrinkles by providing additional matrix structural support.

Biological properties of KTTKs

The most widely used peptide for topical application is KTTKS, which is comprised of five amino acid residues (hence "pentapeptide"). KTTKS is regarded as a "signal peptide" – a short amino acid sequence that possesses the ability to enhance dermal remodelling by triggering cellular processes, such as inhibiting collagenases activities and increasing extracellular matrix (ECM) production. KTTKS is a subfragment of type I collagen propeptide and was discovered in 1993 by a group of researchers at the University of Tennessee. In vitro studies have suggested that amino (-NH2) or carboxyl (-COOH) terminal propeptides of collagen, once removed from their parent procollagen molecules, may exhibit auto-regulatory feedback control of their own synthesis. KTTKS was described as the minimum sequence being able to retain 80% of the original activity of the much larger parent peptide, which is necessary for stimulating ECM synthesis. The stimulatory effect of KTTKS appeared to be specific for collagen type I, type III and fibronectin expressions. However, in vitro studies described the effect as cell density-dependent because it has been shown to be optimal in subconfluent fibroblasts cell culture and gives no response as the cells become fully confluent. Furthermore, the action occurred in both dose- and time-dependent modes and it was found to be neither cell specific nor species-restricted.


Peptides are not new to the world of cosmetics, but their role as cellular messengers is a more recent concept. KTTKS is a small, highly specific and biologically active peptide, which has been reported to produce stimulation of elastin and collagens, specifically types I and III. Pentapeptide-4 activates certain genes involved in the processes of extracellular matrix renewal and cell proliferation. Its 16-carbon aliphatic chain can improve the penetration of the molecule through the lipid structures of the skin. As a result, it can exert good anti-wrinkle and anti-aging effects. It has been used in facial care, body care and eye repair products.


1. Guttman, C. (2002). Studies demonstrate value of procollagen fragment Pal-KTTKS. Dermatology Times, 23(9), 68.

2. Varvaresou, A., Papageorgiou, S., Protopapa, E., & Katsarou, A. (2011). Efficacy and tolerance study of an oligopeptide with potential anti-aging activity. Journal of Cosmetics, Dermatological Sciences and Applications, 1(04), 133.

3. Robinson, 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 1. International journal of cosmetic science, 27(3), 155-160.

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

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