Open AccessBinding of polychlorinated biphenyls to the aryl hydrocarbon receptor.
Author(s) -
Sherif A. Kafafi,
Hussein Y. Afeefy,
Ali H. Ali,
Hakim K. Said,
Abdel G. Kafafi
Publication year - 1993
Publication title -
environmental health perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.257
H-Index - 282
eISSN - 1552-9924
pISSN - 0091-6765
DOI - 10.1289/ehp.93101422
Subject(s) - aryl hydrocarbon receptor , xenobiotic , chemistry , binding affinities , affinities , polychlorinated dibenzo p dioxins , environmental chemistry , aryl , hydrocarbon , dissociation constant , receptor , stereochemistry , organic chemistry , biochemistry , enzyme , transcription factor , alkyl , gene
A new thermodynamic model for calculating the dissociation constants of complexes formed between the aryl hydrocarbon receptor (AhR) and polychlorinated biphenyls (PCBs) is reported. The free energies of binding of PCBs to AhR are controlled by their lipophilicities, electron affinities, and entropies. The corresponding physicochemical properties of polychlorinated dibenzo-p-dioxins and dibenzofurans also control their interactions with AhR. We present evidence supporting the hypothesis that the majority of PCBs are likely to interact with AhR in their nonplanar conformations. In addition, we demonstrate that the affinities of PCBs for AhR relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin correlate with corresponding toxic equivalency factors in animals. The reported methodology is likely to be applicable to other polyhalogenated and mixed polyhalogenated bi- and terphenyls and related xenobiotics; thus, it could minimize the number of in vivo studies in laboratory animals and facilitate the identification of potentially hazardous aromatic xenobiotics.