@article {240,
	title = {Querying the In Vitro Proteome Cysteine Reactivity of 8:2 Fluorotelomer Acrylate.},
	journal = {Environ Sci Technol},
	year = {2023},
	month = {2023 Aug 22},
	abstract = {<p>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 CF-iodoacetamide (F-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-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.</p>},
	issn = {1520-5851},
	doi = {10.1021/acs.est.3c02930},
	author = {Hall, David Ross and Gauthier, Jeremy and Peng, Hui}
}
