human peptide GHK was isolated in 1973 as an activity in human plasma that caused old human liver tissue to synthesize proteins like younger tissue . In human plasma, GHK is present at about 200 micrograms/ litre in men of age 20–25 but declines to 80 micrograms/liter by age 60–80. Subsequent studies established this activity as a tripeptide with an amino acid sequence glycyl-L-histidyl-L-lysine with a strong affinity for copper that readily formed the complex GHK-Cu. Since GHK-Cu promotes cell growth, it was proposed that the GHK acts by delivering copper required for the cellular functions into the cell in a form that is nontoxic and can be utilized by the cell .
The molecular structure of the GHK copper complex (GHK-Cu) has been extensively studied using X-ray crystallography, EPR spectroscopy, X-ray absorption spectroscopy, and NMR spectroscopy as well as other methods such as titration. In the GHK-Cu complex, the Cu (II) ion is coordinated by the nitrogen from the imidazole side chain of the histidine, another nitrogen from the alpha-amino group of glycine, and the deprotonated amide nitrogen of the glycine-histidine peptide bond (Figure 1). Since such a structure could not explain a high stability constant of the GHK-Cu complex (log10 = 16.44 versus 8.68 of the GH copper complex, which is similar to the GHK-Cu structure), it was proposed that another amino group participates in the complex formation. According to the recent study by Bureau et al., the Cu (II) is also coordinated by the oxygen from the carboxyl group of the lysine from the neighbouring complex. Another carboxyl group of lysine from a neighbouring complex provides the apical oxygen, resulting in the square-planar pyramid configuration. Many researchers proposed that, at the physiological pH, GHK-Cu complexes can form binary and ternary structures which may involve amino acid histidine and/or the copper binding region of the albumin molecule. Lau and Sarkar found also that GHK can easily obtain copper 2+ bound to other molecules such as the high-affinity copper transport site on plasma albumin (albumin binding constant log10 = 16.2 versus GHK binding constant 16 log10 = 16.44). It has been established that copper (II) redox activity is silenced when copper ions are complexed with the GHK tripeptide, which allows the delivery of nontoxic copper into the cell