Synthesis of a spin-labeled anti-estrogen as a dynamic motion probe for the estrogen receptor ligand binding domain

J Adam Hendricks; Stefano V Gullà; David E Budil; Robert N Hanson

doi:10.1016/j.bmcl.2011.12.091

Synthesis of a spin-labeled anti-estrogen as a dynamic motion probe for the estrogen receptor ligand binding domain

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1743-6. doi: 10.1016/j.bmcl.2011.12.091. Epub 2012 Jan 8.

Authors

J Adam Hendricks¹, Stefano V Gullà, David E Budil, Robert N Hanson

Affiliation

¹ Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115-5000, United States.

PMID: 22257894
DOI: 10.1016/j.bmcl.2011.12.091

Abstract

The preparation and characterization of a novel nitroxide spin probe based on a steroidal anti-estrogen is described. The probe 5 demonstrated very high binding affinity for both the alpha and beta isoforms of the estrogen receptor-ligand binding domain. EPR spectrometric studies demonstrate conformational constraints for the ligand, consistent with the nitroxyl moiety occupying a position just beyond the receptor-solvent interface.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Electron Spin Resonance Spectroscopy
Estrogen Antagonists / chemical synthesis*
Estrogen Antagonists / chemistry
Estrogen Antagonists / pharmacology
Estrogen Receptor alpha / drug effects
Estrogen Receptor alpha / metabolism*
Ligands
Models, Molecular
Molecular Structure
Nitrogen Oxides / chemistry
Protein Binding / drug effects
Protein Isoforms / metabolism
Protein Structure, Tertiary
Receptors, Estrogen / drug effects
Receptors, Estrogen / metabolism*

Substances

ESR1 protein, human
Estrogen Antagonists
Estrogen Receptor alpha
Ligands
Nitrogen Oxides
Protein Isoforms
Receptors, Estrogen