Polyethylene Glycol Mediated Inhibition of α-Lactalbumin Aggregation: Molecular Insights From a Carbohydrate-Mimicking Stealth Polymer.

Polyethylene glycols (PEG)-assisted strategies for the development of functionalized and compatible carbohydrate polymers are always an exciting topic for polymer research. However, PEGs, a carbohydrate-mimicking stealth polymer, act as a macromolecular crowding agent that has a significant impact on protein aggregation depending on their concentration and molecular weight. The study systematically investigated the impact of PEG molecules with different molecular weights and concentrations on the thermal aggregation of α-Lactalbumin (α-LA). As the concentration was increased from 10 to 200 mg/mL of each PEG molecule (PEG6000, PEG10000, and PEG20000), the β-sheet aggregates and surface hydrophobicity progressively decreased, indicating the aggregation prevention. Spectroscopic and microscopic results showed that PEGs stabilize α-LA toward its native conformation, indicating the modulation of the protein surface. PEG10000 effectively showed its protective role even at its lowest concentration (10 mg/mL), suggesting its potential role in preserving protein stability and functionality. Thus, this study provides potential therapeutics and industrial applications for the prevention of protein aggregation in different environments.