Improvement of Peptidyl Copper Complexes Mimicking Catalase: A Subtle Balance between Thermodynamic Stability and Resistance towards H(2)O(2) Degradation

Catalase mimics are low molecular weight metal complexes that reproduce the activity of catalase, an antioxidant metalloprotein that participates in the cellular regulation of H(2)O(2) concentration by catalyzing its dismutation. H(2)O(2) is a reactive oxygen species that is vital for the normal functioning of cells. However, its overproduction contributes to oxidative stress, which damages cells. Owing to their biocompatibility, peptidyl complexes are an attractive option for clinical applications to regulate H(2)O(2) by enzyme mimics. We report here the synthesis and characterization of four new peptidyl di-copper complexes bearing two coordinating sequences. Characterization of the complexes showed that, depending on the linker used between the two coordinating sequences, their catalytic activity for H(2)O(2) dismutation, their thermodynamic stability and their resistance to H(2)O(2) degradation are very different, with (CATm2)Cu(2) being the most promising catalyst.