GHK (Basic)

GHK (glycyl-L-histidyl-L-lysine; Gly-His-Lys, C14H24N6O4, about 340.38 g/mol) is the free tripeptide without a bound metal ion. It was first isolated as a plasma growth-modulating factor that co-purified with approximately equimolar copper, and its histidyl-lysyl linkage resembles the copper-transport sites of albumin. The free peptide is a naturally occurring high-affinity Cu(II) chelator; when copper is present it binds the metal through its N-terminal amine, a backbone amide nitrogen and the histidine imidazole. In solution the uncomplexed peptide adopts a quasi-folded conformation stabilized by four intramolecular hydrogen bonds.

GHK (Basic) in the research literature

Research on the copper-free peptide has focused on its chemistry as a metal-binding and aldehyde-scavenging molecule. Mass spectrometry, 1H NMR and computational studies showed that GHK forms adducts with the lipid-peroxidation aldehyde 4-hydroxy-2-nonenal at pH 7.4, although it reacted less readily than carnosine. In cell-culture work, GHK bound copper and reduced its redox activity, attenuated copper- and zinc-induced death of central nervous system cells in vitro, and reduced and partially reversed metal-induced aggregation of bovine serum albumin.

The distinction from the copper complex matters in some assays: in dermal fibroblast cultures, the increase in MMP-2 observed with GHK-Cu was reproduced by copper ions but not by GHK alone.