Recent advances in NMR: expanding its role in rational drug design.

The technology of nuclear magnetic resonance spectroscopy continues to advance at a rapid pace. Recent improvements in gradient technology and the coupling of NMR to various chromatography methods will provide new opportunities in drug discovery. These opportunities include rapid high throughput screening to determine the receptor-bound conformations of small organic ligands. NMR coupled to liquid chromatography has opened a new door to the quantitative and qualitative analysis of complex mixtures including metabolites extracted from body fluids and extracts containing various natural products. This review will focus on the following four advances in NMR technology: 1) pulse-field gradient (PFG) NMR, 2) SAR (structure activity relationship) by NMR, 3) LC-NMR (liquid chromatography), and 4) application of membrane models for the study of neuropeptides. The information content available to medicinal chemists from each experiment will be discussed.