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Tytuł pozycji:

Perfluoroalkyl Acid Binding with Peroxisome Proliferator-Activated Receptors α, γ, and δ, and Fatty Acid Binding Proteins by Equilibrium Dialysis with a Comparison of Methods

Tytuł:
Perfluoroalkyl Acid Binding with Peroxisome Proliferator-Activated Receptors α, γ, and δ, and Fatty Acid Binding Proteins by Equilibrium Dialysis with a Comparison of Methods
Autorzy:
Manoochehr Khazaee
Emerson Christie
Weixiao Cheng
Mandy Michalsen
Jennifer Field
Carla Ng
Temat:
equilibrium dialysis
peroxisome proliferator-activated receptors
fatty acid-binding proteins
per- and polyfluorinated alkyl substances
equilibrium dissociation constants
Chemical technology
TP1-1185
Źródło:
Toxics, Vol 9, Iss 3, p 45 (2021)
Wydawca:
MDPI AG, 2021.
Rok publikacji:
2021
Kolekcja:
LCC:Chemical technology
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
2305-6304
Relacje:
https://www.mdpi.com/2305-6304/9/3/45; https://doaj.org/toc/2305-6304
DOI:
10.3390/toxics9030045
Dostęp URL:
https://doaj.org/article/aee8ea50ea614e4e9b578c6c74f183fb  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.8ea50ea614e4e9b578c6c74f183fb
Czasopismo naukowe
The biological impacts of per- and polyfluorinated alkyl substances (PFAS) are linked to their protein interactions. Existing research has largely focused on serum albumin and liver fatty acid binding protein, and binding affinities determined with a variety of methods show high variability. Moreover, few data exist for short-chain PFAS, though their prevalence in the environment is increasing. We used molecular dynamics (MD) to screen PFAS binding to liver and intestinal fatty acid binding proteins (L- and I-FABPs) and peroxisome proliferator activated nuclear receptors (PPAR-α, -δ and -γ) with six perfluoroalkyl carboxylates (PFCAs) and three perfluoroalkyl sulfonates (PFSAs). Equilibrium dissociation constants, KDs, were experimentally determined via equilibrium dialysis (EqD) with liquid chromatography tandem mass spectrometry for protein-PFAS pairs. A comparison was made between KDs derived from EqD, both here and in literature, and other in vitro approaches (e.g., fluorescence) from literature. EqD indicated strong binding between PPAR-δ and perfluorobutanoate (0.044 ± 0.013 µM) and perfluorohexane sulfonate (0.035 ± 0.0020 µM), and between PPAR-α and perfluorohexanoate (0.097 ± 0.070 µM). Unlike binding affinities for L-FABP, which increase with chain length, KDs for PPARs showed little chain length dependence by either MD simulation or EqD. Compared with other in vitro approaches, EqD-based KDs consistently indicated higher affinity across different proteins. This is the first study to report PPARs binding with short-chain PFAS with KDs in the sub-micromolar range.

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