Introduction

Palmitoyl tetrapeptide-7 is a synthetic peptide composed of glutamine, glycine, arginine, and proline amino acids. It is a skin-restoring ingredient and is noted for its soothing ability. It can interrupt factors within the skin that lead to signs of irritation (including from exposure to UVB light) and loss of firmness. By working in this manner, skin can regain a firm feeling and engage in repair, reducing wrinkles visibly[1].

The second most used peptide in 2011 was Palmitoyl Tetrapeptide-7, which was ranked first in 2018. Palmitoyl Tetrapeptide-7 is a fragment of immunoglobulin G. Palmitoyl tetrapeptide-7 decreases IL-6 secretion and reduces inflammation after UVB exposure. It is noteworthy that Palmitoyl Tetrapeptide-7 and Palmitoyl Tripeptide-1 are frequently used together in the ingredient Matrixyl? 3000, which explains the usage percentages in 2018.

Synthesis

Palmitoyl tetrapeptide-7 is a fragment of immunoglobulin G presenting the sequence N-(1-oxohexadecyl)glycyl-L-glutaminyl-L-prolyl-L-arginine. Two different solid-phase methodologies were described for the synthesis of this tetrapeptide. In the first methodology, a preloaded H-Arg(Boc)-HMPB-ChemMatrix resin (29) (functionalized support acylated with Riniker’s super-acid-sensitive (4-hydroxymethyl-3-methoxyphenoxy)butanoic acid handle) is used and the first amino acid is attached by coupling with 2,7-disulfo-9-fluorenylmethoxycarbonyl (Smoc)-proline sodium salt (30). After resin wash and Smoc deprotection, coupling of the next amino acid is performed (Smoc-glutamine (31), and a solution of Smoc-glycine (32)), which was used without side-chain protecting group) until the desired peptide is completed. Oxyma [ethyl 2-cyano-2-(hydroxyimino)acetate] is an additive in the coupling medium that is safer than benzotriazole-based additives such as HOBt. Palmitoylation and cleavage of the peptide from the resin, followed by precipitation and lyophilization, gives the desired palmitoyl tetrapeptide-7[2].

The second methodology involves the presence of a soluble fragment to improve the water solubility of the palmitoyl tetrapeptide-7 so that it is easier to purify. Hence, five hydrophilic lysines are continuously coupled on the amino resin. A connecting arm of p-hydroxybenzoic acid is introduced, and finally, the remaining amino acids are coupled according to the peptide sequence of the palmitoyl tetrapeptide-7 (Pal-Gly-Gln-Pro-Arg-OH). HOBt/DIC methodology is adopted as a coupling approach when other amino acid residues (except the first lysine) are coupled. Removal of the Fmoc protecting groups, resin cleavage, and further purification give the refined peptide hydrolyzed to the target peptide palmitoyl tetrapeptide-7.

References

[1] M. Ferreira. “Trending Anti-Aging Peptides.” Cosmetics (2020).

[2] Diana I S P Resende. “Usage of Synthetic Peptides in Cosmetics for Sensitive Skin.” ACS Applied Energy Materials (2021).