期刊
ENVIRONMENTAL SCIENCE & TECHNOLOGY
卷 55, 期 18, 页码 12291-12301出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.est.1c01200
关键词
alcohols; carboxylic acids; fluorocarbons; perfluorocarbons; protein; sulfonic acids; telomer; thermal stability; toxicokinetic
资金
- National Institute of Environmental Health Sciences of the National Institutes of Health [P42ES031009, T32ES007046]
- NC State University Office of Undergraduate Research Summer Fellowship
This study optimized a novel thermal denaturation assay to evaluate the thermal stability changes of HSA in the presence of various PFAS, revealing the protein-binding properties of most PFAS and providing a new method for understanding the structure and protein-binding properties of these chemicals.
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 (K-d) for each compound were calculated using regression analysis of the dose-dependent changes in HSA melting temperature. Estimated Kd values for HSA binding of octanoic acid, decanoic acid, hexadecenoic acid, ibuprofen, and warfarin agreed with established values. The binding affinities for 24 PFAS that included perfluoroalkyl carboxylic acids (C4-C12), perfluoroalkyl sulfonic acids (C4-C8), mono- and polyether perfluoroalkyl ether acids, and polyfluoroalkyl fluorotelomer substances were determined. These results demonstrate the utility of this differential scanning fluorimetry assay as a rapid high-throughput approach for determining the relative protein-binding properties and identification of chemical structures involved in binding for large numbers of structurally diverse PFAS.
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