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A QSAR evaluation of Ah receptor binding of halogenated aromatic xenobiotics.

Because of their widespread occurrence and substantial biological activity, halogenated aromatic hydrocarbons such as polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzo-p-dioxins (PCDDs) comprise one of the more important classes of contaminants in t...

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Detalles Bibliográficos
Autores principales: Mekenyan, O G, Veith, G D, Call, D J, Ankley, G T
Formato: Texto
Lenguaje:English
Publicado: 1996
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1469544/
https://www.ncbi.nlm.nih.gov/pubmed/9118871
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author Mekenyan, O G
Veith, G D
Call, D J
Ankley, G T
author_facet Mekenyan, O G
Veith, G D
Call, D J
Ankley, G T
author_sort Mekenyan, O G
collection PubMed
description Because of their widespread occurrence and substantial biological activity, halogenated aromatic hydrocarbons such as polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzo-p-dioxins (PCDDs) comprise one of the more important classes of contaminants in the environment. Some chemicals in this class cause adverse biological effects after binding to an intracellular cytosolic protein called the aryl hydrocarbon receptor (AhR). Toxic responses such as thymic atrophy, weight loss, immunotoxicity, and acute lethality, as well as induction of cytochrome P4501A1, have been correlated with the relative affinity of PCBs, PCDFs, and PCDDs for the AhR. Therefore, an important step in predicting the effects of these chemicals is the estimation of their binding to the receptor. To date, however, the use of quantitative structure activity relationship (QSAR) models to estimate binding affinity across multiple chemical classes has shown only modest success possibly due, in part, to a focus on minimum energy chemical structures as the active molecules. In this study, we evaluated the use of structural conformations other than those of minimum energy for the purpose of developing a model for AhR binding affinity that encompasses more of the halogenated aromatic chemicals known to interact with the receptor. Resultant QSAR models were robust, showing good utility across multiple classes of halogenated aromatic compounds.
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spelling pubmed-14695442006-06-01 A QSAR evaluation of Ah receptor binding of halogenated aromatic xenobiotics. Mekenyan, O G Veith, G D Call, D J Ankley, G T Environ Health Perspect Research Article Because of their widespread occurrence and substantial biological activity, halogenated aromatic hydrocarbons such as polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated dibenzo-p-dioxins (PCDDs) comprise one of the more important classes of contaminants in the environment. Some chemicals in this class cause adverse biological effects after binding to an intracellular cytosolic protein called the aryl hydrocarbon receptor (AhR). Toxic responses such as thymic atrophy, weight loss, immunotoxicity, and acute lethality, as well as induction of cytochrome P4501A1, have been correlated with the relative affinity of PCBs, PCDFs, and PCDDs for the AhR. Therefore, an important step in predicting the effects of these chemicals is the estimation of their binding to the receptor. To date, however, the use of quantitative structure activity relationship (QSAR) models to estimate binding affinity across multiple chemical classes has shown only modest success possibly due, in part, to a focus on minimum energy chemical structures as the active molecules. In this study, we evaluated the use of structural conformations other than those of minimum energy for the purpose of developing a model for AhR binding affinity that encompasses more of the halogenated aromatic chemicals known to interact with the receptor. Resultant QSAR models were robust, showing good utility across multiple classes of halogenated aromatic compounds. 1996-12 /pmc/articles/PMC1469544/ /pubmed/9118871 Text en
spellingShingle Research Article
Mekenyan, O G
Veith, G D
Call, D J
Ankley, G T
A QSAR evaluation of Ah receptor binding of halogenated aromatic xenobiotics.
title A QSAR evaluation of Ah receptor binding of halogenated aromatic xenobiotics.
title_full A QSAR evaluation of Ah receptor binding of halogenated aromatic xenobiotics.
title_fullStr A QSAR evaluation of Ah receptor binding of halogenated aromatic xenobiotics.
title_full_unstemmed A QSAR evaluation of Ah receptor binding of halogenated aromatic xenobiotics.
title_short A QSAR evaluation of Ah receptor binding of halogenated aromatic xenobiotics.
title_sort qsar evaluation of ah receptor binding of halogenated aromatic xenobiotics.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1469544/
https://www.ncbi.nlm.nih.gov/pubmed/9118871
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