GHK-Cu is the copper(II) complex of the tripeptide glycyl-L-histidyl-L-lysine (GHK). It is registered under CAS number 49557-75-7 and has a molecular formula of C₁₄H₂₃CuN₆O₄ with a molecular weight of 403.91 g/mol. The peptide was first isolated from human plasma albumin by Loren Pickart in 1973, who identified it as a fragment with growth-promoting activity on hepatocytes in culture.
The copper-binding properties of GHK are central to its biological activity in preclinical models. The histidine residue in the peptide sequence has a high affinity for copper(II) ions, forming a stable complex with a binding constant in the nanomolar range. This copper-binding capacity is thought to underlie several of GHK-Cu's documented effects, as copper is an essential cofactor for numerous enzymes involved in tissue remodeling, including lysyl oxidase (which crosslinks collagen and elastin), superoxide dismutase (an antioxidant enzyme), and cytochrome c oxidase (involved in mitochondrial respiration).
The most extensively documented area of GHK-Cu research concerns wound healing and skin biology. In vitro studies have demonstrated that GHK-Cu promotes the proliferation and migration of dermal fibroblasts, keratinocytes, and endothelial cells. Research has documented upregulation of collagen, elastin, and glycosaminoglycan synthesis in treated fibroblast cultures. Studies examining the molecular mechanisms have identified effects on TGF-β signaling, decorin expression, and matrix metalloproteinase (MMP) regulation — all key components of the extracellular matrix remodeling that occurs during wound healing.
Gene expression research has revealed a broad transcriptional response to GHK-Cu treatment. Studies using microarray and RNA-seq approaches have identified GHK-Cu as a modulator of hundreds of genes involved in tissue remodeling, anti-inflammatory signaling, and antioxidant response. Research published by Pickart and colleagues has documented effects on genes in the TGF-β superfamily, the Wnt signaling pathway, and the NF-κB inflammatory cascade. These broad transcriptional effects have led some researchers to characterize GHK-Cu as a 'tissue remodeling signal' rather than a compound with a single defined mechanism.
Anti-inflammatory research represents a significant area of GHK-Cu investigation. Studies have documented inhibition of TNF-α, IL-6, and IL-1β production in stimulated macrophage cultures. Research has also examined effects on oxidative stress markers, with GHK-Cu demonstrating upregulation of antioxidant enzymes including superoxide dismutase and catalase in treated cells. These anti-inflammatory properties have generated interest in GHK-Cu as a research tool for studying inflammatory pathway modulation.
For in vitro research, GHK-Cu is typically used at concentrations ranging from 1 nM to 10 μM depending on the cell type and endpoint being measured. The compound is supplied as a lyophilized powder and is readily soluble in water. Storage at -20°C is recommended for long-term stability of the lyophilized form.
A complete GHK-Cu COA should confirm the copper content (by ICP-MS or atomic absorption spectroscopy), HPLC purity of the peptide component, and mass spectrometry confirmation of the correct molecular weight.