GHK-Cu is the copper(II) complex of glycyl-L-histidyl-L-lysine, a three-residue peptide first reported from human plasma in the early 1970s. Most of what is firmly established about it is coordination chemistry: how the peptide binds copper, how tightly, and how the complex behaves in solution. This article covers its identity, structure, the laboratory studies in which it has been examined, and general storage. GHK-Cu sold on this site is for laboratory research use only.
What GHK-Cu is
The peptide part, GHK, is written in three-letter code as Gly-His-Lys (H-Gly-His-Lys-OH). All three residues are standard L-amino acids, joined by two peptide bonds:
- Position 1, glycine (G): its free N-terminal amine is one of the copper-binding groups.
- Position 2, histidine (H): its imidazole side chain supplies a second copper-binding nitrogen.
- Position 3, lysine (K): a basic residue carrying the free C-terminal carboxylic acid.
GHK-Cu forms when this tripeptide binds one copper(II) ion. The free peptide and the complex are separate substances with different formulas, masses and CAS numbers, so it matters which one a paper or certificate refers to.
Origin
Pickart and Thaler reported the tripeptide in 1973 after fractionating human serum and testing the fractions in liver-cell cultures (Pickart and Thaler, 1973). In 1980 Pickart and colleagues reported that, during isolation, the peptide co-purified with roughly equimolar copper. They showed that it readily forms a complex with copper(II) and measured copper uptake into a cultured liver-derived cell line in its presence (Pickart et al., 1980; PMID: 7453802).
Chemical identity
| Property | GHK (free peptide) | GHK-Cu (1:1 copper complex) |
|---|---|---|
| Sequence | Gly-His-Lys | Gly-His-Lys with Cu(II) |
| Molecular formula | C14H24N6O4 | C14H22CuN6O4 |
| Average molecular weight | 340.38 g/mol | 401.91 g/mol |
| Monoisotopic mass | 340.1859 Da | 401.0999 Da |
| CAS number | 49557-75-7 | 89030-95-5 |
| PubChem CID | 73587 | 71587328 (CAS-linked record); 10111685 (neutral form) |
| Typical form | Lyophilized (freeze-dried) powder |
All values above come from PubChem. In the neutral complex, the peptide has lost two protons (from the Gly-His amide nitrogen and the carboxylic acid), which balances the 2+ charge of the copper. That gives C14H22CuN6O4 at 401.91 g/mol. PubChem's record linked to CAS 89030-95-5 draws the complex with one extra proton, as the monocation C14H23CuN6O4+ at 402.92 g/mol. Published molecular weights for "GHK-Cu" therefore differ by about one unit, and salt forms differ further.
For mass spectrometry, free GHK gives a singly protonated ion near m/z 341.19, while the singly charged complex appears near m/z 402.11 (copper-63) with a copper-65 peak about two units higher at roughly 45% of its height. That isotope pattern distinguishes the complex from the free peptide.
Copper coordination and structure
Hureau et al., 2011 (Chemistry - A European Journal; PMID: 21780203) characterised the copper(II)-GHK complex with X-ray crystallography, EPR, X-ray absorption and NMR spectroscopy. In solution the complex is monomeric, with three nitrogen donors around the copper: the glycine amine, the deprotonated amide nitrogen between glycine and histidine, and the histidine imidazole nitrogen. The fourth equatorial position is labile. In the solid state a carboxylate oxygen occupies it and the complex is dimeric. The authors also studied ternary complexes with glycine or histidine. By cyclic voltammetry the complex was inert at moderate potentials but could be reduced to copper(I) near -0.62 V (versus Ag/AgCl), releasing the copper ion.
Trapaidze et al., 2012 (Journal of Biological Inorganic Chemistry; PMID: 21898044) measured copper(II) binding by isothermal calorimetry (ITC), using glycine as a weaker competing ligand. They found a predominantly 1:1 peptide-to-copper stoichiometry and a conditional dissociation constant of about 7.0 x 10^-14 M at pH 7.4, placing GHK among the high-affinity copper-binding peptides, with binding driven mainly by enthalpy.
Physicochemical behaviour
Badenhorst et al., 2016 (Pharmaceutical Development and Technology; PMID: 25384620) characterised GHK-Cu with a validated, stability-indicating reversed-phase HPLC method. Measured distribution coefficients (log D) of -2.38 to -2.49 between pH 4.5 and 7.4 show that the complex is highly hydrophilic. It was stable in water and in pH 4.5-7.4 buffers for at least two weeks at 60 C. It underwent hydrolytic cleavage under basic and oxidative stress, and to a lesser extent under acidic stress, with first-order kinetics. HPLC with mass spectrometry identified three main degradation products, one of them free histidine.
Cell-culture studies
One cell-culture paper measured extracellular matrix components in fibroblast cultures:
- Siméon et al., 2000 (Life Sciences) measured matrix metalloproteinase-2 (MMP-2) protein and mRNA in fibroblast cultures, along with secretion of TIMP-1 and TIMP-2. The authors reported that copper ions alone reproduced the MMP-2 change, while copper-free GHK did not. That separates effects of the complex from those of the free peptide.
These are in-vitro measurements in cultured cells. None of them establishes any use in people, and the material described here is not intended for one.
Related: see our GHK-Cu compound page for the catalogue summary.
Storage and handling of lyophilized peptides
GHK-Cu, like most research peptides, is supplied as a lyophilized powder. General laboratory practice for this kind of material:
- Long-term storage: keep sealed vials frozen, commonly at -20 C, away from light.
- Moisture: let a cold vial reach room temperature before opening it so condensation does not form inside, and reseal it promptly.
- Temperature cycling: repeated freezer cycling can speed up degradation, so many labs aliquot material at the outset.
- Records: log the receipt date, storage location and lot reference so results can be traced to a specific batch.
The copper centre adds some specific points. Because copper(II) in the complex can be reduced to copper(I) with release of the metal, solutions are usually kept away from reducing agents and strong oxidants. The stress-testing data above point to keeping solutions near neutral to mildly acidic pH. Additives that bind copper strongly may compete for the metal. A stability-indicating HPLC method can check for degradation products, including free histidine.
For the 100mg strength, the certificate published for lot KVR-2026-20675F reports identity confirmed by RP-HPLC / LC-MS; the measured result is printed on the certificate itself and applies only to that tested lot. Published reports are listed on the Certificates page.
Product details for the material sold on this site are on the GHK-Cu product page.
FAQ
What is GHK-Cu?
GHK-Cu is the copper(II) complex of the tripeptide Gly-His-Lys. The neutral 1:1 complex is C14H22CuN6O4, 401.91 g/mol. It is supplied as a lyophilized powder for laboratory research.
Is GHK-Cu the same as GHK?
No. GHK is the free tripeptide (C14H24N6O4, 340.38 g/mol, CAS 49557-75-7), while GHK-Cu is its copper complex (CAS 89030-95-5).
What has GHK-Cu been studied for in research?
Published work covers its copper coordination structure, copper-binding thermodynamics, redox behaviour, solution stability and degradation products, along with cell-culture studies that measured extracellular matrix proteins and enzymes.
How should lyophilized GHK-Cu be stored?
Sealed vials are commonly kept frozen at around -20 C, protected from light and moisture. Solutions are usually kept near neutral to mildly acidic pH and away from reducing agents, which can reduce and release the copper.
Research use only. Not for human or veterinary use. This article summarises published laboratory research for informational purposes and is not medical advice.
References
- Pickart L, Thaler MM. Nat New Biol. 1973;243(124):85-87. PMID: 4349963.
- Pickart L, Freedman JH, Loker WJ, et al. Nature. 1980;288(5792):715-717. PMID: 7453802. DOI: 10.1038/288715a0
- Hureau C, Eury H, Guillot R, et al. Chemistry. 2011;17(36):10151-10160. PMID: 21780203. DOI: 10.1002/chem.201100751
- Trapaidze A, Hureau C, Bal W, et al. J Biol Inorg Chem. 2012;17(1):37-47. PMID: 21898044. DOI: 10.1007/s00775-011-0824-5
- Badenhorst T, Svirskis D, Wu Z. Pharm Dev Technol. 2016;21(2):152-160. PMID: 25384620. DOI: 10.3109/10837450.2014.979944
- Siméon A, Emonard H, Hornebeck W, Maquart FX. Life Sci. 2000;67(18):2257-2265. PMID: 11045606. DOI: 10.1016/s0024-3205(00)00803-1
Compound data: PubChem CID 73587 (GHK, https://pubchem.ncbi.nlm.nih.gov/compound/73587), CID 71587328 (CAS 89030-95-5 record, https://pubchem.ncbi.nlm.nih.gov/compound/71587328) and CID 10111685 (neutral complex, https://pubchem.ncbi.nlm.nih.gov/compound/10111685).