Steroidal bivalent ligands for the estrogen receptor: design, synthesis, characterization and binding affinities

Bioorg Med Chem. 2009 May 15;17(10):3528-35. doi: 10.1016/j.bmc.2009.04.016. Epub 2009 Apr 12.

Abstract

Steroidal bivalent ligands for the estrogen receptor (ER) were designed using crystal structures of ERalpha dimers as a template. The syntheses of several 17alpha-ethynylestradiol-based bivalent ligands with varying linker compositions and lengths are described. The binding affinities of these bivalent ligands for ERalpha and ERbeta were determined. In the two series of bivalent ligands that we synthesized, there is a clear correlation between linker length and binding affinity, both of which reach a maximum at the same tether length. Further studies are underway to explore aspects of bivalent ligand and control compound binding to the ERs and their effects on ER dimer formation; these results will be reported in a subsequent publication.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Dimerization
  • Drug Design
  • Estrogen Receptor alpha / chemistry*
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / chemistry*
  • Estrogen Receptor beta / metabolism
  • Ethinyl Estradiol / analogs & derivatives*
  • Ethinyl Estradiol / chemical synthesis
  • Ethinyl Estradiol / pharmacology
  • Ligands

Substances

  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Ligands
  • Ethinyl Estradiol