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5024210 
Journal Article 
In vitro and in silico evaluations of binding affinities of perfluoroalkyl substances to baikal seal and human peroxisome proliferator-activated receptor α 
Ishibashi, H; Hirano, M; Kim, EY; Iwata, H 
2019 
Yes 
Environmental Science and Technology
ISSN: 0013-936X
EISSN: 1520-5851 
53 
2181-2188 
English 
In this study, we assessed the binding affinities of perfluoroalkyl substances (PFASs), including perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs), to the ligand-binding domains (LBDs) of Baikal seal ( Pusa sibirica; bs) and human (h) peroxisome proliferator-activated receptor alpha (PPARα). An in vitro competitive binding assay showed that six PFCAs and two PFSAs could bind to recombinant bs and hPPARα LBD proteins in a dose-dependent manner. The relative binding affinities (RBAs) of PFASs to bsPPARα were as follows: PFOS > PFDA > PFNA > PFUnDA > PFOA > PFHxS > PFHpA > PFHxA. The RBAs to bsPPARα showed a significant positive correlation with those to hPPARα. In silico PPARα homology modeling predicted that there were two ligand-binding pockets (LBPs) in the bsPPARα and hPPARα LBDs. Structure-activity relationship analyses suggested that the binding potencies of PFASs to PPARα might depend on LBP binding cavity volume, hydrogen bond interactions, the number of perfluorinated carbons, and the hydrophobicity of PFASs. Interspecies comparison of the in vitro binding affinities revealed that bsPPARα had higher preference for PFASs with long carbon chains than hPPARα. The in silico docking simulations suggested that the first LBP of bsPPARα had higher affinities than that of hPPARα; however, the second LBP of bsPPARα had lower affinities than that of hPPARα. To our knowledge, this is the first evidence showing interspecies differences in the binding of PFASs to PPARαs and their structure-activity relationships. 
• PFDA
     Litsearch Update 5/2019
          PubMed
• PFHpA
     Literature Search Update 2017-2019
          PubMed
• PFHxA
     LitSearch: Feb 2018 - May 2019
          PubMed
          WoS
• PFHxS
     LitSearch: Feb 2018 - May 2019
          PubMed
          WoS
• PFNA
     PFNA May 2019 Update
          Web of Science
          Pubmed
• PFOA (335-67-1) and PFOS (1763-23-1)
     Literature Search Update (2013-2019)
          PubMed
          WOS