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

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.

SUBMITTER: LaFrate AL

PROVIDER: S-EPMC3178464 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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

LaFrate Andrew L AL Carlson Kathryn E KE Katzenellenbogen John A JA

Bioorganic & medicinal chemistry 20090412 10

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 re ...[more]

PMID: 19394231

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