19 F 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 ¹⁹ F- and ¹ H-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 ¹³ C- ¹⁹ F and ¹ H- ¹⁹ F dipolar correlation experiments and permitted characterization of the binding interface. Our results demonstrate that ¹⁹ F MAS NMR is a powerful tool for detailed characterization of protein-ligand interfaces and protein interactions at the atomic level.