Two non-covalently bound antagonists on the human RXR(alpha) LBD protein studied by hydrogen/deuterium exchange and mass spectrometry

摘要

RXRs biological functions can be modulated by interactions with various ligands for clinical treatment of a range of diseases including cancer, diabetes, cardiovascular problems and obesity clinically. Experimental evidence has shown that structurally different ligand can exhibit different gene expression profiles, which is a promising prospect fro reducing adverse effects in the disease treatment or for a variety of other clinical applications. Here, we performed H/D exchange followed by mass spectrometric analysis to probe the specificities of human RXR(alpha) LBD-ligand binding interactions with two antagonists, UVI 2112 and UVI 3003 (Figure 1), and compared the results with the agonist 9-cis-retinoic acid. The knowledge revealed by this approach could help in drug screening and optimization of the structures of synthetic ligands to the RXR(alpha) LBD.