Biophysical characterization of glatiramer acetate (Copaxone): membrane model interactions, vesicle leakage, and secondary structure effects

The synthetic copolymer glatiramer acetate (GA), commercially known as Copaxone, was developed in the 1990s as a treatment for relapsing multiple sclerosis (MS). Recent studies suggest that GA may also exhibit antimicrobial activity. Despite its long-standing clinical use, the molecular mechanism of GA remains poorly understood. Elucidating these mechanisms could facilitate drug repurposing and provide insights into the molecular basis of MS pathology.Here, we employed a range of biophysical techniques to characterize the structural and interaction properties of GA, focusing on its behavior in membrane-mimicking environments such as micelles and large unilamellar vesicles (LUVs). Our results show that GA induces membrane leakage in anionic LUVs, and that GA adopts temperature-dependent secondary structure conformations ranging from α-helical to random coil, which are further influenced by interactions with micelles of different charge. Additionally, GA peptides exhibit an average hydrodynamic radius of approximately 3 nm, and predominantly exist in aggregated rather than monomeric forms.These results highlight the complex structural dynamics of GA and suggest that its biological activity may be closely linked to membrane interactions and peptide aggregation.