NMR spectroscopy in drug discovery: tools for combinatorial chemistry, natural products, and metabolism research.

NMR spectroscopy has enjoyed many advances recently, and the pace of development shows no signs of slowing. This article focuses on advances that have affected solution-state NMR. These advances fall into three general categories: new experimental techniques (new pulse sequence tools), improved hardware and more powerful software. These advances are allowing NMR to help solve important problems in the field of drug discovery. Their impact is widespread. NMR spectroscopy is now being used to determine protein structures, to monitor ligand-receptor binding, to study diffusion, to analyze mixtures using LC-NMR, to analyze solid-phase synthesis resins and to determine the structures of organic small molecules. NMR spectroscopy can provide both qualitative and quantitative information, and can be used in both routine analytical applications and demanding research applications. The applications described here can benefit numerous disciplines in drug discovery, including natural products research, synthetic medicinal chemistry, metabolism studies, drug production, quality control, rational drug design and combinatorial chemistry.