ONE-DIMENSIONAL RELAXATION-EDITED AND DIFFUSION-EDITED NMR METHODS FOR SCREENING COMPOUNDS THAT BIND TO MACROMOLECULES

Two one-dimensional H-1 MMR techniques for efficiently screening Libra ries of compounds for binding to macromolecules are described that exp loit the changes in relaxation or diffusion rates of small molecules w hich occur upon complex formation. The techniques are demonstrated by detecting ligands that bind to the FK506 binding protein and the catal ytic domain of stromelysin in the presence of compounds that do not bi nd to these proteins. These one-dimensional methods detect complex for mation between a ligand and a macromolecule and thus eliminate false p ositives often observed with other techniques. In addition, since thes e methods monitor signals of the uncomplexed compound rather than the bound ligand or macromolecule, ligands for macromolecules of unlimited size can be detected. Furthermore, active compounds can be directly i dentified from a mixture, significantly reducing the time and material needed for screening large libraries of compounds.