Regioselective Protein Oxidative Cleavage Enabled by an Enzyme-like Recognition of an Inorganic Metal Oxo Cluster Ligand

Metal-catalyzed oxidation reactions (MCO) is one of the most applicable methods to induce protein oxidative modifications (e.g., protein oxidation, protein oxidative cleavage and crosslinking), which are essential techniques for many applications in biotechnology and redox proteomics. However, a suitable ligand is needed to assure high stability and enhance the metal catalytic efficiency in order to induce these oxidative modifications in a selective manner. Herein, we report the influence of the polyoxometalates (POMs) as inorganic ligands on the catalytic efficiency of Cu ions to induce oxidative cleavage of a protein. In the presence of ascorbic acid as (Asc), the Cu-substituted POM (Cu-POM), α2-K8P2W17O61(Cu2+.OH2), (CuWD), cleaved hen egg white lysozyme (HEWL), a protein consisting of 129 amino acids, producing only four peptide fragments. Analyzing the intact protein, in absence and presence of CuWD/Asc, and the peptide four peptide fragments via nLC-MS/MS revealed that CuWD/Asc induced oxidative modifications and cleavage at and/or near CuWD/HEWL binding sites