Palmitoyl Tripeptide-8：Bioactivity and Chemical Studies

General description

The Palmitoyl Tripeptide-8, with the CAS No:936544-53-5, is also known as L-Argininamide, N-(1-oxohexadecyl)-L-histidyl-D-phenylalanyl-, This chemical molecular formula is C37H61N9O4 and molecular weight is 695.94. It is a synthetic peptide ester based on a α-melanocyte stimulating hormone (α-MSH), originating from POMC, and it is composed by the sequence N-(1-oxohexadecyl)-L-histidyl-D-phenylalanyl-L-argininamide.[1] The Palmitoyl Tripeptide-8 is a important cosmetic ingredient. The composition of a pool of skin care facial cosmetic products from multinational manufacturers, marketed in Portuguese parapharmacies and pharmacies was collected in 2019, in order to access the most used active ingredients for sensitive skin. According to this study, 88 skin care facial products were selected from 19 multinational brands. Fifteen cosmetic products contained one or more peptides in their composition, making up about 17% of products analyzed. Noteworthy, only two products contained more than one peptide in their composition, and Tripeptide-8 was the common used ingredient in cosmetic products for sensitive skin. Sensitive skin is characterized by symptoms of discomfort when exposed to environmental factors. Peptides are used in cosmetics for sensitive skin and stand out as active ingredients for their ability to interact with skin cells by multiple mechanisms, high potency at low dosage and the ability to penetrate the stratum corneum. And cosmetics with Tripeptide-8 can work for preventing and protecting skin that may exposed to environmental factors.[1] From a chemical perspective, the increasingly use of these peptides as ingredients in the cosmetic industry can be explained as a result of the development of solid-phase syntheses and automated methodologies. Finally, the implementation of reverse-phase high-performance liquid chromatography for peptide purification, in combination with the some factors, has allowed the production of complex peptides in multi-kilogram amounts that was impossible to envisage only a few decades ago and that contributed to a boost in the use of peptides as ingredients in cosmetic formulations.[1]

Figure 1 The molecular formula of Palmitoyl Tripeptide-8

Pharmacodynamics

In vitro, palmitoyl tripeptide-8 showed the ability to significantly inhibit IL-8 production up to 32% in UVBirradiated keratinocytes, which was comparable to α-MSH, and also in IL-1 stimulated fibroblasts, reaching 64% inhibition which is greater that the achieved by α-MSH.[1] In skin explants exposed to substance P, palmitoyl tripeptide-8 significantly reduced the number of dilated capillaries and the size of dilated vessels up to 30% and 51%, respectively. Edema was also reduced by 60% due to palmitoyl tripeptide-8. In areas where palmitoyl tripeptide-8 was applied, a significant reduction in the skin temperature after an increase caused by SDS was found. Together, these results indicate that palmitoyl tripeptide-8 is able to prevent and soothe an irritative respon.[2]

Application

There is one study in the scientific literature show addresses in vivo the efficacy of a formulation containing palmitoyl tripeptide-8 for the treatment of persistent redness in patients with rosacea who had been successfully treated with topical or oral therapy.[4] Applying a lotion containing caffeine, zinc gluconate, bisabolol, Eperua falcata bark extract, and palmitoyl tripeptide-8 for 8 weeks, the evaluation of the product efficacy showed a significant improvement in redness, flushing, skin tone, and overall rosacea severity. Skin radiance, texture, and overall appearance also improved. Regarding patients tolerance, there was a significant improvement in skin erythema, dryness, edema, and stinging. However, the presence of other active ingredients in the product composition and the lack of control do not allow to draw conclusions regarding palmitoyl tripeptide-8 is efficacy. In addition to the cosmetic products found in our investigation, here are also several patented cosmetic formulations for sensitive skin containing palmitoyl tripeptide-8.[5]

Preparation

This peptide can be obtained via a solid-phase peptide synthesis using the fluorenylmethyloxycarbonyl (Fmoc) strategy on an ACT496S2 automated synthesizer with PS-Rink amide (RAM) resin. The deprotection and coupling steps are carried out until the desired sequences are synthesized. Final side-chain deprotection and cleavage from the resin with a cleavage cocktail (trifluoroacetic acid/water/triisopropylsilane), affords palmitoyl tripeptide-8.[3]

Figure 2 Preparation of palmitoyl tripeptide-8.

References

[1]Resende D, Ferreira M S, Sousa-Lobo J M, et al. Usage of Synthetic Peptides in Cosmetics for Sensitive Skin[J]. Pharmaceuticals, 2021.

[2]Loing E. Reaching a Zen-like State in Skin: Biomimetic Peptide to Balance Sensitivity[J].Cosmetics Toiletries.2021.

[3]Martinez J, Verdie P, Dubs P, et al. Tripeptide-Carboxylic acid Conjugates as α-MSH Agonists and Their Therapeutic and Cosmetic Use[P]. FR2870243A1, 19 November 2010.

[4]Baldwin H, Berson D, Vitale M, et al. Clinical effects of a novel topical composition on persistent redness observed in patients who had been successfully treated with topical or oral therapy for papulopustular rosacea.[J]. Drugs Dermatol. 2014, 13, 326–331.

[5]Zhao C, Zhu W, Song X, et al. Anti-Allergic Repair Mask Containing Polypeptide[P]. CN110251415A, 20 September 2019.