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A Study of the Binding of Estradiol and 8-Isoestradiol to the Estrogen α-Receptor by Molecular Modeling

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Abstract

The complexes of the estrogen α-receptor with estradiol and 8-isoestradiol were comparatively analyzed. The computations of ligand–receptor complexes, carried out using the FLEXX program, allowed us to propose a model for the binding of the analogues of 8-isoestradiol. It was found that rings Cand D of estradiol and 8-isoestradiol are similarly arranged in the ligand-binding pocket and coincide upon the superposition of the corresponding ligand–receptor complexes, whereas rings A and B do not coincide. The oxygen functions in position 17 of the estradiol analogues of both series coincide upon superposition, whereas the phenol 3-hydroxyl groups are 0.05 Å apart. A comparison of the predicted biological properties of modified estradiol analogues of the natural and 8-iso-series with the available experimental data revealed their similarity. Synthetic 2-acetyl analogues of 8-isoestrogens were found to have no uterotropic activity, which is also consistent with the proposed model.

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Authors and Affiliations

  1. Chemical Faculty, St. Petersburg State University, Universitetskii pr. 26, Staryi Petergof, St. Petersburg, 198504, Russia

    A. G. Shavva, K. V. Vlasova, S. B. Tsogoeva, M. S. Egorov & P. P. Yakutseni

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  1. A. G. Shavva
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  2. K. V. Vlasova
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  3. S. B. Tsogoeva
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  4. M. S. Egorov
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  5. P. P. Yakutseni
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Shavva, A.G., Vlasova, K.V., Tsogoeva, S.B. et al. A Study of the Binding of Estradiol and 8-Isoestradiol to the Estrogen α-Receptor by Molecular Modeling. Russian Journal of Bioorganic Chemistry 28, 209–214 (2002). https://doi.org/10.1023/A:1015756220637

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