The Expanding Role of NMR in Rational Drug Design

The technology of nuclear magnetic resonance spectroscopy continues to advance at a rapid pace. The development of NMR based rapid high throughput screening methods to identify small organic molecules in complex mixtures that bind to specific protein targets has proven to be an effective method in lead identification. 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 (liquid chromatography) NMR, and 4) application of membrane models for the study of neuropeptide and host defense peptide conformations. The information content available to medicinal chemists from each experiment will be discussed.