Structural requirements of <i>para</i>‐alkylphenols to bind to estrogen receptor
書誌事項
- 公開日
- 1999-05-15
- 権利情報
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- http://onlinelibrary.wiley.com/termsAndConditions#vor
- DOI
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- 10.1046/j.1432-1327.1999.00422.x
- 公開者
- Wiley
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説明
<jats:p>Octyl‐ and nonylphenols in the environment have been proposed to function as estrogens. To gain insight into their structural essentials in binding to the estrogen receptor, a series of phenols with saturated alkyl groups at the <jats:italic>para</jats:italic> position, HO‐C<jats:sub>6</jats:sub>H<jats:sub>4</jats:sub>‐C<jats:sub>n</jats:sub>H<jats:sub>2n+1</jats:sub> (<jats:italic>n</jats:italic> = 0–12), were examined for their ability to displace [<jats:sup>3</jats:sup>H]17β‐estradiol in the recombinant human estrogen receptor, which was expressed in Sf9 cells using the vaculovirus expression system. All tested <jats:italic>para</jats:italic>‐alkylphenols were found to bind fully to the estrogen receptors in a dose‐dependent manner. The interaction of alkylphenols with the receptor became stronger with increase in the number of the alkyl carbons and the activity was maximized with <jats:italic>n</jats:italic> = 9 of nonylphenol. Phenol (<jats:italic>n</jats:italic> = 0) exhibited weak but full binding to the receptor, whereas anisole with a protected phenolic hydroxyl group was completely inactive. Also, alkanes such as <jats:italic>n</jats:italic>‐octane, 2,2,4‐trimethylpentane corresponding to <jats:italic>tert</jats:italic>‐octane, and <jats:italic>n</jats:italic>‐nonane exhibited no binding. The results indicate that the binding of <jats:italic>para</jats:italic>‐alkylphenols to the estrogen receptor is due to the effect of covalent bonding of two constituents of the phenol and alkyl groups, which correspond to the A‐ring and hydrophobic moiety of the steroid structure, respectively. When alkylphenols were examined for their receptor binding conformation by <jats:sup>1</jats:sup>H‐NMR measurements and <jats:italic>ab initio</jats:italic> molecular orbital calculations, it was suggested that nonbranched alkyl groups are in an extended conformation, while branched alkyl groups are in a folded conformation. These results suggest that branched and nonbranched alkyl moieties of alkylphenols interact differently with the lipophilic ligand binding cavity of the estrogen receptor when compared to the binding of 17β‐estradiol.</jats:p>
収録刊行物
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- European Journal of Biochemistry
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European Journal of Biochemistry 262 (1), 240-245, 1999-05-15
Wiley
