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A Kinetic Analysis Of The Conformational Flexibility Of Steroid Hormones, Steven P. Bradbury, Julian Ivanov, Ovanes Mekenyan, Gerritt Schüürmann
A Kinetic Analysis Of The Conformational Flexibility Of Steroid Hormones, Steven P. Bradbury, Julian Ivanov, Ovanes Mekenyan, Gerritt Schüürmann
Steven P. Bradbury
For a set of 10 androgen steroids and estradiol (E2), the kinetic feasibility of conformation flexibility of the cyclic moieties was studied under the constraint of maintaining the B/C trans and C/D trans ring fusion of the natural and biologically active enantiomer. To this end, the conformational energy surface was quantified using the semiempirical quantum chemical AM1 model. The computational analysis included the location of Conformational transition states with associated barriers, and intrinsic reaction coordinate (IRC) calculations to characterize the trajectories of the rotations and the relationships of the transition states to neighbouring chair and twist conformations. Conformational transformations were …
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
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 …