19F Fast Magic-Angle Spinning NMR Spectroscopy on Microcrystalline Complexes of Fluorinated Ligands and the Carbohydrate Recognition Domain of Galectin-3

Structural characterization of protein–ligand binding interfaces at atomic resolution is essential for improving the design of specific and potent inhibitors. Herein, we explored fast 19F- and 1H-detected magic angle spinning NMR spectroscopy to investigate the interaction between two fluorinated ligand diastereomers with the microcrystalline galectin-3 carbohydrate recognition domain. The detailed environment around the fluorine atoms was mapped by 2D 13C–19F and 1H–19F dipolar correlation experiments and permitted characterization of the binding interface. Our results demonstrate that 19F MAS NMR is a powerful tool for detailed characterization of protein–ligand interfaces and protein interactions at the atomic level.