期刊
ENVIRONMENTAL SCIENCE & TECHNOLOGY
卷 57, 期 35, 页码 13015-13024出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.est.3c02930
关键词
PFAS; protein adducts; fluorotelomerpolymers; cysteine reactivity; proteomics
Despite the phase out of traditional PFAS, FTAC remains widely used and poses a threat to health. This study investigates the impact of 8:2 FTAC-modified peptides on protein function and reveals that such modification promotes protein aggregation. These findings shed light on the mechanism of toxicity of PFAS-induced protein aggregation.
Despite the phase out of legacy per- and polyfluoroalkyl substances (PFAS), fluorotelomer-based polymers (FTP) have been used for many applications, notably textile surface coatings. FTPs are of a health concern due to their breakdown into legacy PFAS and the co-occurrence of fluorotelomer acrylate (FTAC) monomers, of which the latter may potentially react with cellular thiols. To evaluate this hypothesis, we employed fluorous-solid-phase extraction (FSPE), to enrich peptides covalently modified by 8:2 fluorotelomer acrylate (8:2 FTAC) and coupled it to a modified nano-liquid chromatography method for the identification of in vitro protein adducts using bottom-up data-dependent proteomics analysis. Using this method, over 100 unique peptides were detected with 8:2 FTAC modifications, although none of the modified cysteine residues were annotated active site nucleophiles. In parallel, a synthetic C6F13-iodoacetamide (F-13-IAM) chemical probe was used to gauge the upper bound of PFAS-thiol reactivity. Over seven hundred peptides were detected with modifications but only 9 of 28 annotated active site cysteines in this dataset were modified by F-13-IAM. Further exploration of the impacts of 8:2 FTAC adducts on protein function revealed that 8:2 FTAC modification promotes protein aggregation in vitro. These results suggest that 8:2 FTAC may exhibit significant proteome thiol reactivity and imply a more general mechanism of toxicity of PFAS-induced protein aggregation.
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