Diffusion edited NMR: Screening compound mixtures by affinity NMR to detect binding ligands to vancomycin

Affinity NMR can be used to produce an edited NMR spectrum that identifies ligands that bind to vancomycin from solution mixtures containing nonbinding molecules. The Diffusion EnCODEd Spectroscopy (DECODES) experiment performed directly on the same sample can be used to determine the: structure of the binding ligands without the need for a physical separation step. The all-D amino acid tetrapeptides DDFA and DDFS, known Ligands for vancomycin, were identified in the presence of eight nonbinding tetrapeptides. The bound-ligand signals in the two-dimensional DECODES spectrum are readily identified by comparison with the spectral patterns of the vancomycin cross-peaks in the 2D total correlation spectroscopy and correlation spectroscopy spectra. The screening of solution mixtures of molecules for direct detection of molecular interactions and structural identification of the interacting ligands provides a powerful new tool to complement methods, such as affinity MS, which rely on the physical separation of mixture components to identify molecular interactions. The solution mixtures of compounds for screening by affinity NMR could come from any source where the components are in similar relative amounts, including synthesis by combinatorial chemistry methods.