Rapid Characterization of Human Serum Albumin Binding for Per- and Polyfluoroalkyl Substances Using Differential Scanning Fluorimetry

Per- and polyfluoroalkyl substances (PFAS) are a diverse class of synthetic chemicals that accumulate in the environment. Many proteins, including the primary human serum transport protein albumin (HSA), bind PFAS. The predictive power of physiologically based pharmacokinetic modeling approaches is currently limited by a lack of experimental data defining albumin-binding properties for most PFAS. A novel thermal denaturation assay was optimized to evaluate changes in the thermal stability of HSA in the presence of increasing concentrations of known ligands and a structurally diverse set of PFAS. Assay performance was initially evaluated for fatty acids and HSA-binding drugs ibuprofen and warfarin. Concentration-response relationships were determined and dissociation constants (