GHK-Cu

GHK-Cu is the copper(II) complex of glycyl-L-histidyl-L-lysine, a tripeptide originally identified in human plasma by Loren Pickart in the early 1970s. The free tripeptide binds copper(II) with high affinity at physiological pH through the imidazole nitrogen of histidine, the N-terminal amine and an intervening amide nitrogen, forming a square-planar complex.

The complex is intensely blue, and that colour is diagnostic: the visible absorbance band arising from the copper d-d transition provides a direct spectrophotometric handle on complex formation and on the copper-to-peptide stoichiometry, which is the parameter most often out of specification in poorly prepared material.

Cultured human dermal fibroblast systems constitute the majority of the in vitro literature. Reported endpoints include collagen and glycosaminoglycan synthesis, proliferation rate, and the balance between matrix metalloproteinases and their tissue inhibitors, which together govern extracellular matrix turnover in these models.

Later transcriptomic work reported that the tripeptide modulates expression across a broad set of genes in cultured cells rather than acting through a single identified receptor, and this breadth of transcriptional effect is a defining and still incompletely explained feature of the compound. Rodent wound models make up much of the remaining in vivo literature.

Verification of this compound differs from that of an ordinary peptide, because the copper complex rather than the free tripeptide is the material of interest. Reversed-phase HPLC establishes peptide purity and mass spectrometry confirms identity, but neither says anything about the copper. Ultraviolet-visible spectrophotometry is the decisive measurement: the copper d-d absorbance band confirms that the complex has formed and allows the copper-to-peptide stoichiometry to be checked directly.

Two impurities matter here and neither appears on a peptide-purity chromatogram. Uncomplexed tripeptide indicates incomplete copper loading; excess free copper salt indicates over-addition, and free copper is redox-active in culture in ways the complex is not. Both are common in poorly prepared material and both are detectable spectrophotometrically, which is why lot documentation for this compound should be read differently from that of a simple peptide.