Physical Sciences and Mathematics Commons^™

Quantitative Structure-Activity Relationships For Polychlorinated Hydroxybiphenyl Estrogen Receptor Binding Affinity: An Assessment Of Conformer Flexibility, Steven P. Bradbury, Ovanes G. Mekenyan, Gerald T. Ankley

Steven P. Bradbury

A diverse group of xenobiotics has a high binding affinity to the estrogen receptor (ER), suggesting that it can accommodate large variability in ligand structure. Relationships between xenobiotic structure, binding affinity, and estrogenic response have been suggested to be dependent on the conformational structures of the ligands. To explore the influence of conformational flexibility on ER binding affinity, a quantitative structure—activity relationship (QSAR) study was undertaken with estradiol, diethylstilbestrol, and a set of polychlorinated hydroxybiphenyls (PCHBs) of environmental concern. Although the low-energy minima of the PCHB congeners suggested that interconversions among conformers were likely, the electronic parameters associated with the …