GHK-Cu: The Copper Tripeptide in Research

GHK-Cu is the copper(II) complex of glycyl-L-histidyl-L-lysine (GHK), a tripeptide identified in human plasma that binds copper with high affinity. In the research literature it has been studied mainly in fibroblast cultures and rat wound-chamber models. That work examined collagen, glycosaminoglycan and matrix metalloproteinase expression, all parts of extracellular matrix turnover. As a lyophilized powder it is blue, which sets it apart from most white research peptides.

Molecular identity

The two identifiers describe different materials. 49557-75-7 is the free tripeptide, while 89030-95-5 is the registry entry for the 1:1 copper complex. Chemical databases also list a separate bis-complex, with two GHK molecules per copper ion, under its own CAS number. When you compare suppliers or COAs, check which form and which molecular weight are being reported. A mass spectrum of GHK-Cu may show the free peptide (340 Da), the copper adduct, or both, depending on ionization conditions.

Discovery and copper binding

GHK was first reported in human blood in 1973. Work published in 1980, when the peptide was abbreviated GHL, described it as a plasma tripeptide and found that it co-isolated with roughly equimolar copper. The authors pointed out its resemblance to the copper-binding site of albumin, where copper binds a histidine next to a basic residue. They reported that the tripeptide readily forms complexes with copper(II) and increases copper uptake into cultured hepatoma cells, which led them to propose GHK as a physiological copper carrier [1].

GHK also occurs inside larger proteins. The sequence is present in the α2(I) chain of type I collagen [2]. Proteolysis of SPARC, a matrix-associated protein, releases GHK and the related KGHK. In that study the angiogenic activity mapped mainly to KGHK and longer peptides and did not require prior incubation with copper [3]. These findings are the basis for the idea, discussed in the literature, that GHK can be released from the extracellular matrix during proteolysis [2, 3].

What the research has examined

Collagen synthesis in fibroblast cultures

In fibroblast cultures, GHK-Cu stimulated collagen synthesis. The effect began at picomolar concentrations, peaked near 10⁻⁹ M, and was independent of changes in cell number [2].

Glycosaminoglycan synthesis

In normal human fibroblast cultures, GHK-Cu increased the synthesis of sulfated glycosaminoglycans. The response was biphasic: stimulation was greatest at 10⁻⁹ to 10⁻⁸ M and returned toward control levels at higher concentrations. It preferentially increased extracellular dermatan sulfate and cell-associated heparan sulfate, with no effect on hyaluronic acid synthesis [4].

Matrix metalloproteinases in rat wound models

In a rat wound-chamber model, GHK-Cu was examined for effects on matrix metalloproteinases (MMPs). Interstitial collagenase activity was unchanged. MMP-9 expression persisted longer in GHK-Cu chambers, and pro-MMP-2 and activated MMP-2 were higher at later time points. The authors concluded that the complex modulates MMP expression at different stages of matrix remodeling [5].

Proteoglycans in rat wound models

In the same model system, GHK-Cu increased wound-chamber tissue mass, type I collagen and glycosaminoglycan content. It changed the expression of the small proteoglycans decorin and biglycan differently, and it also raised decorin expression in dermal fibroblast cultures [6].

Reviews

A 2008 review by one of the peptide's original investigators summarizes the wider body of GHK and GHK-Cu work under the heading of tissue remodeling [7]. Like any single-author review, it is best read alongside the primary papers above.

Analytical notes

GHK is a small, polar tripeptide. On reverse-phase HPLC it elutes early in the gradient, so the method needs enough early retention to separate it from the solvent front and from small impurities. Free copper, excess peptide and the bis-complex are all possible components of a GHK-Cu preparation, so the COA should state how purity and identity were determined. See HPLC purity explained and reading a certificate of analysis. Batch documents are in the COA registry.

The blue color is useful as an identity check. A GHK-Cu vial, or a blend containing a substantial amount of it, should look blue. A white powder sold as GHK-Cu points to a problem with the copper complex.

In blends

GHK-Cu is the largest component by mass in two blends we carry: 50 mg of the 80 mg KLOW vial and 50 mg of the 70 mg GLOW vial (Made in USA lots: KLOW, GLOW). See the KLOW blend overview and KLOW vs GLOW for how it sits alongside BPC-157, TB-500 and KPV.

Common questions

Is GHK the same as GHK-Cu?

No. GHK is the free tripeptide (340.38 Da, CAS 49557-75-7). GHK-Cu is its copper(II) complex (about 402.9 Da, CAS 89030-95-5). Several of the fibroblast and wound-model studies above used the copper complex specifically [2, 4, 5, 6]. Results for one form shouldn't be assumed for the other.

Why is GHK-Cu called a copper peptide?

Because the copper is part of the material. GHK binds copper(II) readily, and early work proposed it as a carrier of copper into cultured cells [1].

Storage and handling

Store lyophilized GHK-Cu at −20 °C, away from light and moisture, and let the vial reach room temperature before opening. After reconstitution, keep the solution at 2–8 °C and avoid repeated freeze–thaw cycles. Note any visible change in color in your records. Handle it as laboratory material throughout.

The single-compound vial is available as GHK-Cu.

References

1. Pickart L, et al. Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells. Nature. 1980. PubMed
2. 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
3. Lane TF, et al. SPARC is a source of copper-binding peptides that stimulate angiogenesis. J Cell Biol. 1994. PubMed
4. Wegrowski Y, et al. Stimulation of sulfated glycosaminoglycan synthesis by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. Life Sci. 1992. PubMed
5. Siméon A, et al. Expression and activation of matrix metalloproteinases in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+. J Invest Dermatol. 1999. PubMed
6. Siméon A, et al. Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+). J Invest Dermatol. 2000. PubMed
7. Pickart L. The human tri-peptide GHK and tissue remodeling. J Biomater Sci Polym Ed. 2008. PubMed