ABSTRACT
The lack of suitable tools for the identification of potential drug leads from complex matrices is a bottleneck in drug discovery. Here, we report a novel method to screen complex matrices for new drug leads targeting transmembrane receptors. Using α3ß4 nicotinic receptors as a model system, we successfully demonstrated the ability of this new tool for the specific identification and effective extraction of binding compounds from complex mixtures. The formation of cell-membrane coated nanoparticles was confirmed by transmission electron microscopy. In particular, we have developed a direct tool to evaluate the presence of functional α3ß4 nicotinic receptors on the cell membrane. The specific ligand binding to α3ß4 nicotinic receptors was examined through ligand fishing experiments and confirmed by high-performance liquid chromatography coupled with diode-array detection and electrospray ionization mass spectrometry. This tool has a great potential to transform the drug discovery process focusing on identification of compounds targeting transmembrane proteins, as more than 50% of all modern pharmaceuticals use membrane proteins as prime targets.
Subject(s)
Cell Membrane/chemistry , Chromatography, High Pressure Liquid , Ferric Compounds/chemistry , Metal Nanoparticles/chemistry , Pharmaceutical Preparations/chemistry , Receptors, Nicotinic/metabolism , Spectrometry, Mass, Electrospray Ionization , HEK293 Cells , Humans , Ligands , Microscopy, Electron, Transmission , Nicotine/analysis , Pharmaceutical Preparations/analysis , Receptors, Nicotinic/chemistry , Smoke/analysis , Tobacco Products/analysisABSTRACT
Intimate partner violence (IPV) affects countless women and men in lesbian, gay, and bisexual (LGB) as well as heterosexual relationships, but few studies have examined how such abuse is associated with the mental health of LGB victims. The present study addresses this issue using data from the 2006 Behavioral Risk Factor Surveillance System (BRFSS) survey to examine differences in depression and anxiety among IPV victims in LGB and heterosexual partnerships. The findings indicate LGB IPV victims are much more likely to have a history of depression (OR 1.70, p < .05) and anxiety (OR 1.70, p < .05) than heterosexual victims. These differences are slightly mediated by the victim's perceived emotional support but not the type of abuse experienced. Our findings accentuate the need for greater inclusion of LGB persons in the IPV and mental health discourse, as well as the importance of social support for IPV victims. Policy implications for members of the LGB community are discussed.
