Journal article
Mechanistic insights into the specificity of human cytosolic sulfotransferase 2A1 (hSULT2A1) for hydroxylated polychlorinated biphenyls through the use of fluoro-tagged probes
Environmental science and pollution research international, Vol.23(3), pp.2119-2127
02/2016
DOI: 10.1007/s11356-015-4886-8
PMCID: PMC4713379
PMID: 26165989
Abstract
Determining the relationships between the structures of substrates and inhibitors and their interactions with drug-metabolizing enzymes is of prime importance in predicting the toxic potential of new and legacy xenobiotics. Traditionally, quantitative structure activity relationship (QSAR) studies are performed with many distinct compounds. Based on the chemical properties of the tested compounds, complex relationships can be established so that models can be developed to predict toxicity of novel compounds. In this study, the use of fluorinated analogues as supplemental QSAR compounds was investigated. Substituting fluorine induces changes in electronic and steric properties of the substrate without substantially changing the chemical backbone of the substrate. In vitro assays were performed using purified human cytosolic sulfotransferase hSULT2A1 as a model enzyme. A mono-hydroxylated polychlorinated biphenyl (4-OH PCB 14) and its four possible mono-fluoro analogues were used as test compounds. Remarkable similarities were found between this approach and previously published QSAR studies for hSULT2A1. Both studies implicate the importance of dipole moment and dihedral angle as being important to PCB structure in respect to being substrates for hSULT2A1. We conclude that mono-fluorinated analogues of a target substrate can be a useful tool to study the structure activity relationships for enzyme specificity.
Details
- Title: Subtitle
- Mechanistic insights into the specificity of human cytosolic sulfotransferase 2A1 (hSULT2A1) for hydroxylated polychlorinated biphenyls through the use of fluoro-tagged probes
- Creators
- E J Ekuase - Department of Pharmaceutical Sciences and Experimental Therapeutics, The University of Iowa, Iowa City, IA, USAT J van 't Erve - Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, 27709, NC, USA. thomas.vanterve@nih.govA Rahaman - Department of Chemistry, The University of Iowa, Iowa City, IA, USAL W Robertson - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USAM W Duffel - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA, USAG Luthe - LuthePharma, Fabrikstrasse 2, 48599, Gronau, Germany
- Resource Type
- Journal article
- Publication Details
- Environmental science and pollution research international, Vol.23(3), pp.2119-2127
- DOI
- 10.1007/s11356-015-4886-8
- PMID
- 26165989
- PMCID
- PMC4713379
- NLM abbreviation
- Environ Sci Pollut Res Int
- ISSN
- 0944-1344
- eISSN
- 1614-7499
- Publisher
- Germany
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01 CA038683 / NCI NIH HHS P30 ES05605 / NIEHS NIH HHS P42 ES013661 / NIEHS NIH HHS
- Language
- English
- Date published
- 02/2016
- Academic Unit
- Occupational and Environmental Health; Pharmaceutical Sciences and Experimental Therapeutics; Iowa Superfund Research Program; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984002351002771
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