DIFFUSION EDITED NMR - SCREENING COMPOUND MIXTURES BY AFFINITY NMR TODETECT BINDING LIGANDS TO VANCOMYCIN

Affinity NMR can be used to produce an edited NMR spectrum that identi fies ligands that bind to vancomycin from solution mixtures containing nonbinding molecules. The Diffusion EnCODEd Spectroscopy (DECODES) ex periment performed directly on the same sample can be used to determin e the: structure of the binding ligands without the need for a physica l separation step. The all-D amino acid tetrapeptides DDFA and DDFS, k nown Ligands for vancomycin, were identified in the presence of eight nonbinding tetrapeptides. The bound-ligand signals in the two-dimensio nal DECODES spectrum are readily identified by comparison with the spe ctral patterns of the vancomycin cross-peaks in the 2D total correlati on spectroscopy and correlation spectroscopy spectra. The screening of solution mixtures of molecules for direct detection of molecular inte ractions and structural identification of the interacting ligands prov ides a powerful new tool to complement methods, such as affinity MS, w hich rely on the physical separation of mixture components to identify molecular interactions. The solution mixtures of compounds for screen ing by affinity NMR could come from any source where the components ar e in similar relative amounts, including synthesis by combinatorial ch emistry methods.