N-Prolyl Palmitoyl Tripeptide-56 Acetate

N‑Prolyl Palmitoyl Tripeptide‑56 Acetate is a synthetic matrikine lipopeptide with firming and anti-aging properties, known under the trade name (used in peptide-based complex) Matrixyl® Morphomics™. Its structure is not linear like in regular peptides; here, proline is grafted on the terminal nitrogen of lysine in Pal‑Lys(Pro)‑His‑Gly and stabilized with acetic acid.

N‑Prolyl Palmitoyl Tripeptide‑56 Acetate was identified through screening of 120 candidate peptides tested in human dermal fibroblast cultures, where it showed the most promising results in stimulating the production of extracellular matrix components.

According to the manufacturer, N‑Prolyl Palmitoyl Tripeptide‑56 Acetate enhances the expression and production of collagen types I, III, IV, and VI, as well as fibronectin, which are essential components of the extracellular matrix. It also enhances the production of structural components responsible for dermal cell-to-matrix adhesion, including Cofilin, α-Actinin-1, Actin, Talin, Integrins α2/β1, and Fibronectin.

LC‑MS/MS and complementary biochemical assays confirmed that the peptide significantly impacts two pathways: one regulating collagen production and another the actin cytoskeleton. Moreover, it upregulates transcription factors such as FOXO and stress-response proteins, including sestrins, both of which are linked to cellular longevity and collagen regulation.

In vitro tests on normal human dermal fibroblasts showed increased collagen and fibronectin at both the gene and protein levels, indicating that the peptides act as a matrikine. These findings suggest that N‑Prolyl Palmitoyl Tripeptide‑56 Acetate not only increases ECM density but also reorganizes fibers, thereby improving skin structure. In vivo test with human volunteers revealed a significant reduction of marionette, frown, and vertical lines, as well as a visible decrease in crow's feet after six weeks of application, without significant adverse effects.