文摘
Two one-dimensional 1H NMR techniques for efficientlyscreening libraries of compounds for binding tomacromolecules are described that exploit the changes in relaxation ordiffusion rates of small molecules whichoccur upon complex formation. The techniques are demonstrated bydetecting ligands that bind to the FK506 bindingprotein and the catalytic domain of stromelysin in the presence ofcompounds that do not bind to these proteins.These one-dimensional methods detect complex formation between aligand and a macromolecule and thus eliminatefalse positives often observed with other techniques. In addition,since these methods monitor signals of theuncomplexed compound rather than the bound ligand or macromolecule,ligands for macromolecules of unlimitedsize can be detected. Furthermore, active compounds can bedirectly identified from a mixture, significantly reducingthe time and material needed for screening large libraries ofcompounds.