GHK-Cu and AHK-Cu: Copper Peptides in Dermal and Hair-Follicle Research

Copper tripeptides are among the most studied peptides in dermal biology. GHK-Cu is the original and best documented; AHK-Cu is a close analogue studied mainly in hair-follicle models. Both are copper(II) complexes, and their chemistry matters as much as their biology.

GHK-Cu: a plasma tripeptide

Glycyl-L-histidyl-L-lysine (GHK) was first isolated from human plasma by Loren Pickart and binds copper(II) with high affinity. Plasma GHK levels are reported to decline with age.

• Collagen: GHK-Cu stimulated collagen synthesis in fibroblast cultures at nanomolar concentrations (Maquart et al., 1988).
• Matrix remodelling: it is reported to modulate both matrix metalloproteinases and their inhibitors (TIMPs).
• Gene expression: Connectivity Map analyses suggest GHK influences the expression of a large number of human genes, including repair- and antioxidant-related sets (reviewed by Pickart & Margolina, 2018).

AHK-Cu: the hair-follicle analogue

Alanyl-L-histidyl-L-lysine copper (AHK-Cu) has been studied mainly in follicle biology. In cultured human hair follicles, AHK-Cu promoted follicle elongation ex vivo and the proliferation of dermal papilla cells, while reducing markers of apoptosis (Pyo et al., 2007).

Copper chemistry at the bench

• Colour check: copper(II)–peptide complexes are blue to violet in solution; a colourless solution suggests the copper is missing or displaced.
• Avoid chelators: EDTA and other strong chelators in buffers strip copper from the peptide — use chelator-free media for treatment arms.
• Stoichiometry: confirm the peptide-to-copper ratio on the certificate, since excess free copper is cytotoxic and confounds viability assays.
• Controls: include the copper-free peptide and an equivalent copper salt so the effect can be attributed to the complex.