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Title: Interactions of sterols with antiestrogen-binding sites: structural requirements for high-affinity binding
Authors: Hwang, P.L.H. 
Matin, A.
Issue Date: 1989
Citation: Hwang, P.L.H., Matin, A. (1989). Interactions of sterols with antiestrogen-binding sites: structural requirements for high-affinity binding. Journal of Lipid Research 30 (2) : 239-245. ScholarBank@NUS Repository.
Abstract: Animal and human tissues contain a microsomal protein that binds nonsteroidal antiestrogens with high affinity and specificity. The functions of these binding sites and the identity of their natural ligands are unknown. Following a report that certain sterols inhibit [3H]tamoxifen binding to this site, we attempted to define the structural requirements for maximal inhibition of [3H]tamoxifen binding to rat liver antiestrogen-binding sites. Our studies identified 5α-cholestan-3β-ol-7-one (7-ketocholestanol) as the most potent sterol, having an inhibitory activity that was 12% that of unlabeled tamoxifen and an equilibrium dissociation constant of 6.3 nM. Structural features that appeared important for the inhibitory activity of this sterol include the presence of i) a hydrocarbon side chain at C17; ii) an oxygen function at C7; iii) a hydroxyl group at C3; and iv) the absence of a double-bond between C5 and C6. Saturation analysis and kinetic studies of [3H]tamoxifen binding in the presence of varying concentrations of 7-ketocholestanol clearly indicated that this sterol competed directly with tamoxifen for the antiestrogen-binding site. Unlike tamoxifen, this sterol did not bind to the estrogen receptor. These features make 7-ketocholestanol a potentially valuable tool for studying the properties and functions of this site.
Source Title: Journal of Lipid Research
ISSN: 00222275
Appears in Collections:Staff Publications

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