Structure of estradiol metal chelate and estrogen receptor complex: the basis for designing a new class of selective estrogen receptor modulators.

Abstract

Selective estrogen receptor modulators, such as 17β-estradiol derivatives bound to metal complexes, have been synthesized as targeted probes for the diagnosis and treatment of breast cancer. Here, we report the detailed 3D structure of estrogen receptor α ligand-binding domain (ERα-LBD) bound with a novel estradiol-derived metal complex, estradiol-pyridine tetra acetate europium(III), at 2.6 Å resolution. This structure provides important information pertinent to the design of novel functional ERα targeted probes for clinical applications.

• Authors: Min-Jun Li, Harry M Greenblatt, Orly Dym, Shira Albeck, Adi Pais, Chidambaram Gunanathan, David Milstein, Hadassa Degani, Joel L Sussman
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 54 Issue 10 Pg. 3575-80 (May 26 2011) ISSN: 1520-4804 [Electronic] United States
• PMID: 21473635 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Chelating Agents
• ESR1 protein, human
• Estrogen Receptor alpha
• Ligands
• Metals
• Selective Estrogen Receptor Modulators
• Europium
• Estradiol

Topics

• Chelating Agents (chemistry)
• Chemistry, Pharmaceutical (methods)
• Crystallography, X-Ray (methods)
• Dimerization
• Estradiol (chemistry)
• Estrogen Receptor alpha (antagonists & inhibitors)
• Europium (chemistry)
• Humans
• Ligands
• Metals (chemistry)
• Models, Chemical
• Molecular Conformation
• Protein Binding
• Protein Structure, Tertiary
• Selective Estrogen Receptor Modulators (chemistry, pharmacology)