A di-Copper Peptidyl Complex Mimics the Activity of Catalase, a Key Antioxidant Metalloenzyme

Catalases (CAT) are antioxidant metalloenzymes necessary for life in oxygen-metabolizing cells to regulate H₂O₂ concentration by accelerating its dismutation. Many physiopathological situations are associated with oxidative stress resulting from H₂O₂ overproduction, during which antioxidant defenses are overwhelmed. We have used a combinatorial approach associated with an activity-based screening to discover a first peptidyl di-copper complex mimicking CAT. The complex was studied in detail and characterized for its CAT activity both in solutions and in cells using different analytical methods. The complex exhibited CAT activity in solutions and, more interestingly, on HyPer HeLa cells that possess a genetically encoded ratiometric fluorescent sensors of H₂O₂. These results highlight the efficiency of a combinatorial approach for the discovery of peptidyl complexes that exhibit catalytic activity.