Steroidal bivalent ligands for the estrogen receptor: design, synthesis, characterization and binding affinities.
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.
LaFrate
Andrew L
AL
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S. Mathews Ave., Urbana, IL 61801, USA.
Carlson
Kathryn E
KE
Katzenellenbogen
John A
JA
D019281:Dimerization; D015195:Drug Design; D047628:Estrogen Receptor alpha / Q000737:chemistry* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000737:chemistry* / Q000378:metabolism; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008024:Ligands
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D004997:Ethinyl Estradiol