(19)F NMR viewed through two different lenses: ligand-observed and protein-observed (19)F NMR applications for fragment-based drug discovery

(19)F NMR has emerged as a powerful tool in drug discovery, particularly in fragment-based screens. The favorable magnetic resonance properties of the fluorine-19 nucleus, the general absence of fluorine in biological settings, and its ready incorporation into both small molecules and biopolymers, has enabled multiple applications of (19)F NMR using labeled small molecules and proteins in biophysical, biochemical, and cellular experiments. This review will cover developments in ligand-observed and protein-observed (19)F NMR experiments tailored towards drug discovery with a focus on fragment screening. We also cover the key advances that have furthered the field in recent years, including quantitative, structural, and in-cell methodologies. Several case studies are described for each application to highlight areas for innovation and to further catalyze new NMR developments for using this versatile nucleus.