Receptor interactions by polybrominated diphenyl ethers versus polychlorinated biphenyls: A theoretical structure–activity assessment

Gregor Luthe; James A Jacobus; Larry W Robertson

doi:10.1016/j.etap.2007.10.017

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Receptor interactions by polybrominated diphenyl ethers versus polychlorinated biphenyls: A theoretical structure–activity assessment

Journal article

Peer reviewed

Receptor interactions by polybrominated diphenyl ethers versus polychlorinated biphenyls: A theoretical structure–activity assessment

Gregor Luthe, James A Jacobus and Larry W Robertson

Environmental toxicology and pharmacology, Vol.25(2), pp.202-210

2008

DOI: 10.1016/j.etap.2007.10.017

PMCID: PMC2746664

PMID: 19768137

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http://doi.org/10.1016/j.etap.2007.10.017View

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Abstract

The extensive body of literature regarding the interaction of polychlorinated biphenyls (PCBs) with transcription factors (receptors) has great value to understand similarities and distinctions and in formulating hypotheses regarding the activity of polybrominated diphenyl ethers (PBDEs) toward those same receptors. Our goal is to present the most comprehensive overview of PBDE effects on AhR, CAR, PXR, ER, AR, PR, DHT, TH, T3, T4 and IGF, as well as hypothetical biological activities of PPAR, RyR, GR and GABA. Aside the influence of the conformation of the ligand, we discuss its constitution influencing the binding affinity: size and polarizability, hydrophilicity, Gibbs free energy of solvation, inductive and mesomeric effects. We evaluate the techniques to determine the biologically relevant conformation of these halogenated hydrocarbons, including computation methods, X-ray and microwave spectroscopy. A novel fluoro-tagged ligand approach holds promise as tools for illuminating the steric and electronic effects in ligand–receptor interaction. Based on our assessment, we predict that PBDEs do not exhibit AhR activity themselves, but impurities are responsible for these effects.

PCBs

Mesomeric effects

Polarizability

PBDEs

IGF

AhR

RyR

PXR

Binding affinity

Gibbs free solvation energy

Inductive effects

DHT

Polybrominated diphenyl ethers

PPAR

Hydrophilicity

CAR

Polychlorinated biphenyls

GABA

Conformation

Constitution

Details

Title: Subtitle: Receptor interactions by polybrominated diphenyl ethers versus polychlorinated biphenyls: A theoretical structure–activity assessment
Creators: Gregor Luthe - Department of Occupational and Environmental Health, University of Iowa, 100 Oakdale Campus # 124 IREH, Iowa City, IA 52242-5000, USA
James A Jacobus - Department of Occupational and Environmental Health, University of Iowa, 100 Oakdale Campus # 124 IREH, Iowa City, IA 52242-5000, USA
Larry W Robertson - Department of Occupational and Environmental Health, University of Iowa, 100 Oakdale Campus # 124 IREH, Iowa City, IA 52242-5000, USA
Resource Type: Journal article
Publication Details: Environmental toxicology and pharmacology, Vol.25(2), pp.202-210
DOI: 10.1016/j.etap.2007.10.017
PMID: 19768137
PMCID: PMC2746664
NLM abbreviation: Environ Toxicol Pharmacol
ISSN: 1382-6689
eISSN: 1872-7077
Publisher: Elsevier B.V
Language: English
Date published: 2008
Academic Unit: Occupational and Environmental Health; Iowa Superfund Research Program
Record Identifier: 9984001101402771

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