NMR Reporter Screening for the Detection of High-Affinity Ligands

Binding is good, displacing is better. By adding a weakly binding reporter ligand to a mixture of protein and test compounds, NMR screening can identify strongly binding ligands by observing the displacement of the reporter ligand. For example, NMR screening identified, as a reporter ligand, a small fragment, 2-acetylbenzofuran (1, gray skeleton), which binds to the active site of 3α-HSD. A molecular model of the complex between 3α-HSD and 1 is shown.