Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.
Inorg Chem. 2020 Aug 17;59(16):11218-11222. doi: 10.1021/acs.inorgchem.0c01193. Epub 2020 Jul 27.
Degradation of saccharides is relevant to the design of catalytic therapeutics, the production of biofuels, inhibition of biofilms, as well as other applications in chemical biology. Herein, we report the design of multinuclear Cu complexes that enable cleavage of saccharides under physiological conditions. Reactivity studies with -nitrophenyl (NP)-conjugated carbohydrates show that dinuclear Cu complexes exhibit a synergistic effect and promote faster and more robust cleavage of saccharide substrates, relative to the mononuclear Cu complex, while no further enhancement is observed for the tetranuclear Cu complex. The use of scavengers for reactive oxygen species confirms that saccharide cleavage is promoted by the formation of superoxide and hydroxyl radicals through Cu redox chemistry, similar to that observed for native copper-containing lytic polysaccharide monooxygenases (LMPOs). Differences in selectivity for di- and tetranuclear Cu complexes are modest. However, these are the first reported small multinuclear Cu complexes that show selectivity and reactivity against mono- and disaccharide substrates and form a basis for further development of metalloglycosidases for applications in chemical biology.
糖的降解与催化治疗、生物燃料生产、生物膜抑制以及化学生物学的其他应用有关。在此，我们报告了多核 Cu 配合物的设计，这些配合物可在生理条件下切割糖。用-硝基苯基（NP）-缀合的碳水化合物进行反应性研究表明，双核 Cu 配合物表现出协同作用，相对于单核 Cu 配合物，更能促进糖底物的更快和更有力的切割，而四核 Cu 配合物则没有进一步的增强。使用活性氧种的清除剂证实，糖的切割是通过 Cu 氧化还原化学形成超氧阴离子和羟自由基来促进的，类似于天然含铜溶菌酶（LMPOs）的情况。双核和四核 Cu 配合物对选择性的差异不大。然而，这些是首批报道的对单糖和二糖底物具有选择性和反应性的小分子多核 Cu 配合物，为进一步开发用于化学生物学的金属糖苷酶奠定了基础。
