Polyethylene-glycol-modified zwitterionic polymer assisted protein aggregation arrest and refolding

Abstract

Protein aggregation limits the development of protein-based drugs, and leads to neurological disorders. In this study, the zwitterionic polymer, poly-sulfobetaine (p-SPB), was modified using polyethylene glycol (PEG), and exhibited the remarkable suppression of heat-induced lysozyme aggregation. The study revealed that the modified polymers prevented the formation of amyloid fibrils, and retained the enzymatic activity of lysozyme, which is lost after heating. An increase in the molecular weight of the polymers afforded higher efficacy to perpetuate enzymatic activity. Along with the effectiveness of these polymers for lysozyme aggregation arrest, further evaluations revealed that these polymers facilitated the refolding of the protein because of their tendency to dissolve the already formed fibrils, and regained the lost lysozyme activity. These findings suggest that the amalgamation of PEG and p-SPB has the potential to protect proteins from aggregation via altering the hydrophobic environment of the lysozyme, creating a molecular shield around the protein molecules, and thus, providing scope for the development of protein-based biopharmaceuticals.