Angewandte Chemie International Edition · 2002 · 99 citations · 0 references
PharmacyMolecular BiologyDrug DiscoveryMolecular RecognitionStructural BiologyLigand BindingProtein-ligand BindingProtein-ligand InteractionsProtein-ligand RecognitionReceptor-ligand InteractionsSmall-molecule ScreeningActive Site AnalysisAffinity ScreeningBinding AssaysLigand Binding AnalysisLigand ScreeningLigand-binding AssaysProtein-ligand Binding AssaysReceptor-ligand Binding
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.