[Molecular model of binding of estradiol and 8-isoestradiol with estrogen alpha-receptor]

Bioorg Khim. 2002 May-Jun;28(3):236-41.
[Article in Russian]

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.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cholesterol / blood
  • Estradiol / analogs & derivatives*
  • Estradiol / chemistry*
  • Estradiol / metabolism
  • Estradiol / pharmacology
  • Estrogen Receptor alpha
  • Female
  • Isomerism
  • Ligands
  • Models, Molecular
  • Organ Size
  • Ovariectomy
  • Rats
  • Receptors, Estrogen / chemistry*
  • Receptors, Estrogen / metabolism
  • Structure-Activity Relationship
  • Triglycerides / blood
  • Uterus / drug effects

Substances

  • Estrogen Receptor alpha
  • Ligands
  • Receptors, Estrogen
  • Triglycerides
  • Estradiol
  • Cholesterol