A beginner's guide to 19F NMR and its role in drug screening

Abstract

The structural biology renaissance has created new opportunities for both understanding mechanisms of action of many dynamic protein complexes and advancing drug discovery. 19F NMR can play a key role in both protein and ligand nuclear magnetic resonance (NMR). In particular, by judiciously labeling the protein target with CF3 reporters, functional states can be monitored as a function of ligand or drug candidate so as to understand their mechanism of action or response. At the same time, fragment-based drug discovery (FBDD) using fluorinated libraries enables the rapid detection of binders and their elaboration toward lead compounds. Future studies will likely employ fluorinated tags with improved chemical shift sensitivity and reporters that can be biosynthetically incorporated via AMBER stop codon technologies. At the same time, FBDD will be greatly improved by promising new fluorinated libraries in combination with improved computational methods for predicting lead compounds.