Journal article
Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin
Environmental science & technology, Vol.50(10), pp.5320-5327
05/17/2016
DOI: 10.1021/acs.est.6b00484
PMCID: PMC4883002
PMID: 27116425
Abstract
The disposition of toxicants is often affected by their binding to serum proteins, of which the most abundant in humans is serum albumin (HSA). There is increasing interest in the toxicities of environmentally persistent polychlorinated biphenyls (PCBs) with lower numbers of chlorine atoms (LC-PCBs) due to their presence in both indoor and outdoor air. PCB sulfates derived from metabolic hydroxylation and sulfation of LC-PCBs have been implicated in endocrine disruption due to high affinity-binding to the thyroxine-carrying protein, transthyretin. Interactions of these sulfated metabolites of LC-PCBs with HSA, however, have not been previously explored. We have now determined the relative HSA-binding affinities for a group of LC-PCBs and their hydroxylated and sulfated derivatives by selective displacement of the fluorescent probes 5-dimethylamino-1-naphthalenesulfonamide and dansyl-l-proline from the two major drug-binding sites on HSA (previously designated as Site I and Site II). Values for half-maximal displacement of the probes indicated that the relative binding affinities were generally PCB sulfate ≥ OH-PCB > PCB, although this affinity was site- and congener-selective. Moreover, specificity for Site II increased as the numbers of chlorine atoms increased. Thus, hydroxylation and sulfation of LC-PCBs result in selective interactions with HSA which may affect their overall retention and toxicity.
Details
- Title: Subtitle
- Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin
- Creators
- Eric A Rodriguez - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa , Iowa City, Iowa 52246, United StatesXueshu Li - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52246, United StatesHans-Joachim Lehmler - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52246, United StatesLarry W Robertson - Department of Occupational and Environmental Health, College of Public Health, The University of Iowa , Iowa City, Iowa 52246, United StatesMichael W Duffel - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa , Iowa City, Iowa 52246, United States
- Resource Type
- Journal article
- Publication Details
- Environmental science & technology, Vol.50(10), pp.5320-5327
- DOI
- 10.1021/acs.est.6b00484
- PMID
- 27116425
- PMCID
- PMC4883002
- NLM abbreviation
- Environ Sci Technol
- ISSN
- 0013-936X
- eISSN
- 1520-5851
- Publisher
- United States
- Grant note
- P42 ES013661 / NIEHS NIH HHS P30 ES005605 / NIEHS NIH HHS P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 05/17/2016
- Academic Unit
- Occupational and Environmental Health; Iowa Neuroscience Institute; Pharmaceutical Sciences and Experimental Therapeutics; Iowa Superfund Research Program; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984001090602771
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