GHK Peptide, Urocanic Acid, and Copper Form New Physiological Complex

The tripeptide GHK (Gly-His-Lys), cis-urocanic acid (cis-UCA), and Cu(II) ions are naturally occurring components found in human tissues like the skin and plasma. While GHK is well-established as a Cu(II)-binding molecule with various biological effects, the potential for cis-UCA to also coordinate Cu(II), and more importantly, whether these two ligands can form a ternary complex with Cu(II) in physiological settings, remained unexplored.

The study definitively confirmed that cis-urocanic acid is indeed capable of coordinating Cu(II) ions, establishing it as a novel copper-binding ligand. Crucially, the researchers successfully identified and characterized the formation of a stable ternary Cu(II) complex involving all three components: GHK, cis-UCA, and Cu(II), demonstrating their simultaneous interaction. This newly identified [GHK][Cu(II)][cis-urocanic acid] ternary complex is likely a physiologically relevant species, given the natural concentrations and reported affinities of its constituents in human tissues like skin and plasma. The formation of this complex suggests a novel mechanism by which GHK and cis-UCA might exert their known biological effects, potentially by modulating Cu(II) availability and activity. This finding provides a deeper understanding of Cu(II) homeostasis and the intricate interactions of these biomolecules.