Enzymes offer numerous advantages as catalysts, such as selectivity and stereocontrol. However, their practical use is constrained by various limitations, including low thermal stability, low tolerance to diverse experimental conditions, and expensive processes of preparation and purification. To address these challenges, the development of enzyme mimics aims to mitigate these weaknesses. Enzyme mimics (EMs) are typically developed to replicate the binding and catalytic functions of natural enzymes, employing two primary methods: either mimicking enzyme activity through metal complexes with comparable properties, or reproducing the structure of the enzyme active site by means of suitable functional groups, such as oligopeptides [1,2]. Our approach in designing novel enzyme mimics integrates both strategies and relies on synthetic branched peptides to generate a previously unexplored category of EMs. A biocompatible central scaffold serves as the core of the EM structure, to which various oligopeptides can be attached (one for each maleimide chain, Figure 1) [3,4]. In this work we aimed at replicating the catalytic sites of metalloenzymes by introducing specific amino acid sequences capable of binding active metal ions. For instance, various surrogates of Cu/Zn-SOD, Fe/Mn-SOD, and Ni-SOD can be synthesized. Thermodynamic, spectroscopic and structural studies of single peptides and/or tetrabranched systems and their 100 metal complexes (e.g. Cu, Mn, Ni) will be 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.
Design and study of metal complexes with tetrabranched peptide systems as surrogates of superoxide dismutase
Denise BELLOTTI;Silvia LEVERARO;Maurizio REMELLI;
2024
Abstract
Enzymes offer numerous advantages as catalysts, such as selectivity and stereocontrol. However, their practical use is constrained by various limitations, including low thermal stability, low tolerance to diverse experimental conditions, and expensive processes of preparation and purification. To address these challenges, the development of enzyme mimics aims to mitigate these weaknesses. Enzyme mimics (EMs) are typically developed to replicate the binding and catalytic functions of natural enzymes, employing two primary methods: either mimicking enzyme activity through metal complexes with comparable properties, or reproducing the structure of the enzyme active site by means of suitable functional groups, such as oligopeptides [1,2]. Our approach in designing novel enzyme mimics integrates both strategies and relies on synthetic branched peptides to generate a previously unexplored category of EMs. A biocompatible central scaffold serves as the core of the EM structure, to which various oligopeptides can be attached (one for each maleimide chain, Figure 1) [3,4]. In this work we aimed at replicating the catalytic sites of metalloenzymes by introducing specific amino acid sequences capable of binding active metal ions. For instance, various surrogates of Cu/Zn-SOD, Fe/Mn-SOD, and Ni-SOD can be synthesized. Thermodynamic, spectroscopic and structural studies of single peptides and/or tetrabranched systems and their 100 metal complexes (e.g. Cu, Mn, Ni) will be 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.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
