Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Elemental isomerism: A boron-nitrogen surrogate for a carbon-carbon double bond increases the chemical diversity of estrogen receptor ligands

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Zhou, H. B.
  • Nettles, Kendall
  • Bruning, John
  • Kim, Y.
  • Joachimiak, A.
  • Sharma, S.
  • Carlson, K. E.
  • Stossi, F.
  • Katzenellenbogen, B. S.
  • Greene, G. L.
  • Katzenellenbogen, J. A.

publication date

  • June 2007

journal

  • Chemistry & Biology  Journal

abstract

  • To increase the chemical diversity of bioactive molecules by incorporating unusual elements, we have examined the replacement of a C=C double bond with the isoelectronic, isostructural B-N bond in the context of nonsteroidal estrogen receptor (ER) ligands. While the B-N bond was hydrolytically labile in the unhindered cyclofenil system, the more hindered anilino dimesitylboranes, analogs of triarylethylene estrogens, were easily prepared, hydrolytically stable, and demonstrated substantial affinity for ERs. X-ray analysis of one ERalpha-ligand complex revealed steric clashes with the para methyl groups distorting the receptor; removal of these groups resulted in an increase in affinity, potency, and transcriptional efficacy. These studies define the structural determinants of stability and cellular bioactivity of a B-N for C=C substitution in nonsteroidal estrogens and provide a framework for further exploration of "elemental isomerism" for diversification of drug-like molecules.

subject areas

  • Boron
  • Carbon
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Estrogens, Non-Steroidal
  • Humans
  • Isomerism
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Nitrogen
  • Protein Binding
  • Radioligand Assay
  • Receptors, Estrogen
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 1074-5521

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2007.04.009

PubMed ID

  • 17584613
scroll to property group menus

Additional Document Info

start page

  • 659

end page

  • 669

volume

  • 14

issue

  • 6

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support