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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.

rsc chemical biology

<sup>19</sup>F NMR viewed through two different lenses: ligand-observed and protein-observed<sup>19</sup>F NMR applications for fragment-based drug discovery

19F NMR viewed through two different lenses: ligand-observed and protein-observed19F NMR applications for fragment-based drug discovery

¹⁹F NMR viewed through two different lenses: ligand-observed and protein-observed¹⁹F NMR applications for fragment-based drug discovery