Tissue biology · GHK-Cu
GHK-Cu: fifty years of copper-peptide research
October 20, 2026 · 2 min read · Models: Cell culture, Rodent
GHK (glycyl-L-histidyl-L-lysine) is a tripeptide first isolated from human plasma in 1973 that binds copper(II) with high affinity. Cell-culture studies associate the copper complex with collagen and glycosaminoglycan synthesis in fibroblasts, and gene-expression analyses have linked it to broad changes in transcription.
A summary of published research for scientific reference. It is not medical advice and does not describe or endorse use in humans or animals. Findings from cell culture and animal models often do not carry over to other systems.
Discovery
Loren Pickart identified GHK as a factor in human plasma that altered the behavior of cultured liver cells (Pickart and Thaler, Nature New Biology, 1973). The tripeptide was later shown to form a tight complex with Cu²⁺. Much of its biological activity in vitro is attributed to that copper complex.
Fibroblast and extracellular-matrix studies
Maquart and colleagues (FEBS Letters, 1988) reported that GHK-Cu stimulated collagen synthesis in fibroblast cultures at nanomolar concentrations. Later work extended this to glycosaminoglycans and to the balance of matrix metalloproteinases and their inhibitors, and rodent models have been used to study its effects on angiogenesis and matrix remodeling.
Gene-expression analyses
Using the Broad Institute’s Connectivity Map, Pickart and colleagues reported that GHK shifts the expression of a large number of human genes in cell-line data. These include genes involved in DNA repair, antioxidant defense and the ubiquitin–proteasome system. The analyses are hypothesis-generating: Connectivity Map profiles come from a few cancer cell lines at fixed concentrations, and they need targeted follow-up.
Practical considerations for in-vitro work
Because activity depends on copper binding, the ratio of peptide to copper, buffer composition and competing chelators (such as EDTA or albumin in serum-containing media) can change results. Reporting these conditions makes studies easier to compare.
References
- Pickart L, Thaler MM. Tripeptide in human serum which prolongs survival of normal liver cells and stimulates growth in neoplastic liver. Nat New Biol. 1973;243:85–87.
- Maquart FX, Pickart L, Laurent M, et al. Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. FEBS Lett. 1988;238(2):343–346.
- Pickart L, Vasquez-Soltero JM, Margolina A. GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration. Biomed Res Int. 2015;2015:648108.