Probing the Binding of Propranolol Enantiomers to α1-Acid Glycoprotein with Ligand-Detected NMR Experiments

Mapping the interactions of a small molecule ligand with a protein can provide information important for biochemical studies and for drug design and development. This information can be determined using the ligand-detected H-1 NMR experiments T-1 rho-NOESY, diffusion, and saturation transfer difference (STD). This work compares the results of these experiments and examines their ability to distinguish the binding epitopes of propranolol enantiomers with alpha(1)-acid glycoprotein (AGP). The epitope maps for the propranolol enantiomers are fairly similar, as expected from their similar binding affinities; however, the STD epitope maps provide unique insights into the different orientations of the enantiomers with respect to the AGP binding pocket. Our results suggest that it is best to consider the data provided by several NMR epitope mapping experiments in drawing conclusions about ligand-protein binding interactions.