Design and characterization of metal/tetrabranched peptide adducts as possible superoxide dismutase mimics

Enzymes offer numerous advantages as catalysts, such as selectivity and stereocontrol. However, their use is limited by some restrictions, including low thermal and chemical stability, low adaptation to extreme environments, and expensive preparation and purification processes. To address these challenges, enzyme mimics (EMs) can be used. EMs typically replicate the binding and catalytic activities of natural enzymes, employing two primary methods: 1) mimicking enzyme activity through metal complexes with comparable properties, 2) reproducing the active site structure by means of suitable functional groups, such as oligopeptides [1,2]. We integrated both strategies to produce an EM based on a synthetic branched scaffold (Figure 1) able to bind metal-binding peptides [3,4]. In particular, to replicate the catalytic sites of Cu/Zn-, Fe/Mn- and Ni-superoxide dismutases, we design specific amino acid sequences capable of binding active metal ions. Thermodynamic, spectroscopic and structural studies of single peptides and/or tetrabranched systems and their complexes with Cu have been carried out, together with the investigation of their redox behaviour and catalytic activity. Financial support of the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.1 – NextGenerationEU (PRIN PNRR 2022 - P2022EMY52) is gratefully acknowledged.