Tuning Au Reactivity Beyond Canonical Targets: Ligand-Driven Au(I) Metalation of Lysine Residues in Hen Egg White Lysozyme

Au(I) complexes are widely investigated as therapeutic agents due to their high affinity for biological nucleophiles and protein targets. Here, the reactivity of an Auranofin (AF) derivative bearing naproxen as a ligand toward hen egg white lysozyme (HEWL) was investigated by a combined crystallographic and computational approach. Notably, the first observation of lysine metalation in HEWL by an Au complex is reported. The results highlight how ligand substitution can significantly affect Au(I) reactivity toward biomacromolecules, enabling noncanonical targeting and potentially impacting biological activity.