GHK-Cu

GHK-Cu is the 1:1 complex of the tripeptide Gly-His-Lys (one-letter GHK) with a Cu(II) ion. The free peptide has the molecular formula C14H24N6O4 and average mass 340.38 Da; the copper complex carries the approximate formula C14H22CuN6O4 with an average mass near 402.9 Da. CAS registries: GHK-Cu 89030-95-5; free GHK 49557-75-7.

Copper coordination is square-planar: Cu(II) binds the N-terminal α-amine, the deprotonated amide nitrogen of the Gly-His bond, and the imidazole nitrogen of histidine, with the lysine side chain projecting away from the chelation site. This geometry is the basis for the characteristic visible-region absorbance band that confirms complex formation by UV-Vis.

The peptide portion is produced by standard Fmoc solid-phase synthesis — a short, well-behaved tripeptide with no inherently difficult couplings. Most of the analytical risk lives in the chelation step rather than the synthesis:

• Off-stoichiometry complexes. Under- or over-copperization yields 2:1 (peptide-rich) and 1:2 (copper-rich) species that have different solubility and UV-Vis profiles than the 1:1 specification.
• Free GHK and free copper salts. Incomplete complexation, or post-formation dissociation under low pH or strong chelators, leaves uncomplexed peptide and copper that a label may not distinguish from authentic GHK-Cu.
• Trace-metal contamination. Fe(III), Zn(II), and Ni(II) compete with copper for the GHK chelation site; the residual-metals screen has to look beyond copper alone.
• Histidine oxidation and minor dipeptide truncations (GH, HK) from the peptide step.

The standard CertikLabs panel for a GHK-Cu batch:

• RP-HPLC purity of the peptide component (C18, low-TFA buffer, UV 220 nm)
• LC-MS identity of free GHK (theoretical [M+H]+ 341.18)
• UV-Vis spectroscopy for the characteristic Cu(II)-peptide d–d band near 525 nm to confirm complex formation
• ICP-MS or ICP-OES for total copper content and trace-metal screen
• Stoichiometry check (mol Cu : mol peptide) against the 1:1 specification

A defensible GHK-Cu certificate must report the peptide purity, the observed copper content, and the resulting peptide:Cu molar ratio. The Certificate of Analysis includes the UV-Vis spectrum so the d–d band can be confirmed by anyone holding the document.

Published literature describes effects on wound repair, extracellular matrix remodeling, antioxidant activity, and modulation of copper-dependent enzymes. The copper coordination is essential — the apo-peptide GHK has substantially different activity than the GHK-Cu complex.

Primary sources:

• Pickart L., Margolina A., Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data.(PMID 29462900)
• Pickart L. et al., GHK peptide as a natural modulator of multiple cellular pathways in skin regeneration.(PMID 26236730)

CertikLabs does not publish dosing, administration routes, or clinical recommendations for GHK-Cu.

Solid GHK-Cu is generally stable refrigerated and protected from light. In aqueous solution the complex is pH-sensitive (the Cu(II) coordination requires the imidazole and α-amine to be deprotonated); strongly acidic conditions dissociate the complex, and prolonged storage in solution can shift the peptide:Cu ratio. Analytical re-test of any working solution is the only reliable confirmation.