<br>19F NMR 揭示了全氟烷基物质（PFAS）与白蛋白的显性熵结合,Chemosphere

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19F NMR 揭示了全氟烷基物质（PFAS）与白蛋白的显性熵结合
Chemosphere ( IF 8.1 ) Pub Date : 2020-09-02 , DOI: 10.1016/j.chemosphere.2020.128083
Michael Fedorenko ₁ , Jessica Alesio ₁ , Anatoliy Fedorenko ₁ , Angela Slitt ₂ , Geoffrey D Bothun ₁

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了解多氟烷基和全氟烷基物质（PFAS）与蛋白质结合的机制对于了解 PFAS 在体内的分布和积累以及开发 PFAS 类别内和跨类别 PFAS 的预测模型至关重要。氟核磁共振波谱（19F NMR）已被证明是研究 PFAS 结合的一种强大但未得到充分利用的工具;每个氟基团的化学位移反映了沿 PFAS 分子长度的局部环境。使用牛血清白蛋白（BSA），我们报告了四种常见 PFAS 的解离常数 Kd，远低于报告的临界胶束浓度（CMC） - 全氟辛酸（PFOA）、全氟壬酸（PFNA）、全氟己烷磺酸（PFHxS）和全氟辛烷磺酸（PFOS） - 作为磷酸盐缓冲盐水中温度的函数。根据与阴离子头基相邻的二氟乙基和末端三氟甲基测定 Kd 值。我们的结果表明，相对于头部基团，疏水尾部表现出更大的结合亲和力，并且结合亲和力与之前的结果基本一致，表明更大的 PFAS 疏水性导致更大的蛋白质结合。然而，结合机制以熵疏水相互作用为主，这归因于 PFAS 尾部在蛋白质疏水腔内和蛋白质表面的脱溶剂。此外，PFNA 似乎在低于报告的 CMC 值的蛋白质表面形成半半球。这项工作为利用 19F NMR 进行 PFAS 蛋白结合研究提供了一种新方法，并为溶剂熵的作用提供了新的视角。

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Dominant entropic binding of perfluoroalkyl substances (PFASs) to albumin protein revealed by 19F NMR

Mechanistic insight into protein binding by poly- and perfluoroalkyl substances (PFASs) is critical to understanding how PFASs distribute and accumulate within the body and to developing predictive models within and across classes of PFASs. Fluorine nuclear magnetic resonance spectroscopy (19F NMR) has proven to be a powerful, yet underutilized tool to study PFAS binding; chemical shifts of each fluorine group reflect the local environment along the length of the PFAS molecule. Using bovine serum albumin (BSA), we report dissociation constants, Kd, for four common PFASs well below reported critical micelle concentrations (CMCs) − perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS) − as a function of temperature in phosphate buffered saline. Kd values were determined based on the difluoroethyl group adjacent to the anionic headgroups and the terminal trifluoromethyl groups. Our results indicate that the hydrophobic tails exhibit greater binding affinity relative to the headgroup, and that the binding affinities are generally consistent with previous results showing that greater PFAS hydrophobicity leads to greater protein binding. However, the binding mechanism was dominated by entropic hydrophobic interactions attributed to desolvation of the PFAS tails within the hydrophobic cavities of the protein and on the surface of the protein. In addition, PFNA appears to form hemimicelles on the protein surfaces below reported CMC values. This work provides a renewed approach to utilizing 19F NMR for PFAS-protein binding studies and a new perspective on the role of solvent entropy.

更新日期：2020-09-02

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