Unlocking complexity through neutron scattering: Structure and dynamics of protein-polymer conjugates

Protein-polymer conjugates are engineered to enhance the pharmacokinetics and stability of biopharmaceuticals. This review delves into the structural and dynamic characteristics of protein-polymer conjugates, employing advanced techniques such as neutron scattering, circular dichroism, and fluorescence spectroscopy. Here, we focus on model proteins like maltose-binding protein (MBP), bovine serum albumin (BSA), and myoglobin (Mb) conjugated with hydrolysable polyphosphoesters (PPEs) to generate fully degradable polymer-protein conjugates. The study underscores the influence of factors such as the polymers' molar mass, grafting density, hydration levels, and deuteration on protein stability, flexibility, and thermal properties. The study demonstrates that the degree of polymerization, solvation properties, and isotopic composition play crucial roles in determining the behavior of protein-polymer complexes. In particular, neutron scattering techniques are invaluable in unraveling the interaction mechanisms, providing valuable insights that can inform the optimization of protein-polymer conjugates for therapeutic applications.