What is Copper peptide?

A copper peptide is a short peptide carrying a bound copper(II) ion. Many peptides chelate copper, but in the research and cosmetic-science literature the term almost always means GHK-Cu, the complex of the tripeptide glycyl-L-histidyl-L-lysine with Cu2+. GHK was first reported in 1973 as a factor in human serum that prolonged the survival of normal liver cells ^[1], and it was later characterised as a plasma tripeptide with affinity for copper(II) ^[2]. Chemical databases also list it as copper tripeptide-1 and prezatide copper.

The molecule

GHK is Gly-His-Lys with free termini: C14H24N6O4, 340.38 Da as the free peptide (calculated from the sequence). The same Gly-His-Lys triplet occurs in the α2(I) chain of type I collagen, which led to the suggestion that the tripeptide could be released by proteases at wound sites ^[2]. The copper complex is a different species with its own stoichiometry and protonation state, discussed below.

How copper binds

Crystal and solution studies show that GHK and the albumin N-terminal sequence DAHK, both high-affinity Cu(II) chelators found in plasma, bind copper quite differently ^[3]:

The open fourth site allows ternary complexes, for example with glycine or histidine ^[3]. Potentiometric titration across pH 3.5–10.6 found several binary species and extensive ternary complexes with histidine, and showed that the lysine ε-amino group raises complex stability compared with Gly-His or Gly-His-Gly ^[4].

Competition with albumin

In equilibrium dialysis at pH 7.5, GHK held about 42% of the Cu(II) when present at the same concentration as albumin; under physiological concentrations of copper, albumin, histidine and peptide, about 6% of the copper sat with the low-molecular-weight components ^[4]. Later work identified ternary Cu(GHK)–albumin complexes formed through albumin His3 (conditional binding constant 2900 M−1 at pH 7.4) and a second histidine ^[5].

How the term is used in research

In fibroblast cultures, GHK-Cu stimulated collagen synthesis from 10−12 to 10−11 M, with a maximum at 10−9 M and no change in cell number ^[2]. A 2018 review co-authored by GHK's discoverer collates reported effects on collagen, elastin and glycosaminoglycan synthesis and on fibroblast behaviour ^[6]; such summaries are best read alongside the primary studies they draw on, such as the cell-culture collagen data above. The picomolar-to-nanomolar range in the fibroblast work sits many orders below a typical stock concentration, so accurate serial dilution, for example with the dilution calculator, matters more than usual.

Points of confusion

• Formula and mass depend on how the complex is drawn. PubChem lists GHK-Cu records at 400.90 and 402.92 g/mol, differing in protonation and charge. For molar calculations use the composition in the batch documentation, including any counter-ion, rather than either database value.
• Speciation follows pH. The species present shift across the pH range ^[4], so buffer choice changes what is actually in the well.
• Colour is chemistry, not contamination. Cu(II)–peptide complexes absorb visible light, which is how their formation was followed spectrophotometrically ^[4]; the GHK-Cu product page lists available sizes.