title: [Molecular model of binding of estradiol and 8-isoestradiol with estrogen alpha-receptor].
abstract: The complexes of the estrogen alpha-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 C and 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 A apart. A comparison of the predicted biological properties of modified estradiol analogues of the natural and 8-isoseries 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.
authors.affiliation: Chemical Faculty, St. Petersburg State University, Universitetskii pr. 26, Staryi Petergof, St. Petersburg, 198504 Russia. nmr@paloma.spbu.ru
authors.forename: A G
authors.initials: AG
authors.lastname: Shavva
authors.forename: K V
authors.initials: KV
authors.lastname: Vlasova
authors.forename: S B
authors.initials: SB
authors.lastname: Tsogoeva
authors.forename: M S
authors.initials: MS
authors.lastname: Egorov
authors.forename: P P
authors.initials: PP
authors.lastname: Iakutseni
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005260:Female; D007536:Isomerism; D008024:Ligands; D008958:Models, Molecular; D009929:Organ Size; D010052:Ovariectomy; D051381:Rats; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000097:blood; D014599:Uterus / Q000187:drug effects
chemical_list: D047628:Estrogen Receptor alpha; D008024:Ligands; D011960:Receptors, Estrogen; D014280:Triglycerides; D004958:Estradiol; D002784:Cholesterol