GHK-Cu — Published Research

GHK binds copper(II) with a stability constant (log K) of approximately 16.2, among the highest for biological copper-binding molecules. The coordination geometry involves the amino terminus, the histidine imidazole nitrogen, and deprotonated amide nitrogens. NMR and X-ray crystallography studies show a square-planar coordination. The high copper affinity suggests GHK may function in copper transport and delivery to tissues. Plasma GHK levels are approximately 200 ng/mL in young adults, decreasing with age.

Pickart L, Margolina A. “Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data.” Int J Mol Sci. 2018. PMC

Microarray analyses using the Broad Institute Connectivity Map database identified that GHK modulates the expression of numerous genes involved in extracellular matrix remodeling, including upregulation of collagen types I and III, elastin, and decorin genes, and downregulation of metalloproteinases. The mechanism appears to involve activation of the integrin receptor complex and downstream focal adhesion kinase signaling, as well as effects on TGF-β pathway genes in dermal fibroblast cultures.

Pickart L et al. “GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration.” Biomed Res Int. 2015. PubMed

In vivo wound healing studies in rat and pig models demonstrated that GHK-Cu increased the rate of wound closure, collagen deposition, and angiogenesis as measured by vessel density and VEGF expression. The copper moiety appears essential for full activity, as apo-GHK (without copper) showed reduced effects. Mechanistic studies suggest GHK-Cu activates copper-dependent enzymes including lysyl oxidase (collagen crosslinking) and superoxide dismutase (SOD).

Maquart FX et al. “Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.” FEBS Lett. 1988. PubMed