Structure-based design of estrogen receptor-beta selective ligands

We present the structure-based optimization of a series of estrogen receptor-beta (ERbeta) selective ligands. X-ray cocrystal structures of these ligands complexed to both ERalpha and ERbeta are described. We also discuss how molecular modeling was used to take advantage of subtle differences between the two binding cavities in order to optimize selectivity for ERbeta over ERalpha. Quantum chemical calculations are utilized to gain insight into the mechanism of selectivity enhancement. Despite only two relatively conservative residue substitutions in the ligand binding pocket, the most selective compounds have greater than 100-fold selectivity for ERbeta relative to ERalpha when measured using a competitive radioligand binding assay.     

Room-temperature,excitation wavelength-dependent fluorescence at surfaces: a potential method for studying the micro-heterogeneity of surface environments

The fluorescence maxima at room temperature of 5-dimethylamino-1-naphthalenesulfonamide (dansylamide) groups covalently attached to the surface of silica particles in dry form and slurried in acetonitrile exhibit varying degrees of dependence upon excitation wavelength. This dependence is attributed to the micro-heterogeneity of the surface itself and varying degrees of accessibility of the fluorophore to solvent. The observed effect may prove useful in investigations of surface environment heterogeneity at the molecular level.