Abstract
Pharmaceutical and academic nuclear magnetic resonance (NMR) groups have implemented NMR screening techniques as a powerful approach to identify and to investigate protein/ligand interactions. Pharmaceutical groups in particular have incorporated NMR screening strategies into their drug discovery and drug design programs. This stems from the fact that NMR screening is naturally synergistic with combinatorial or medicinal chemistry, high throughput screening (HTS), structure-based drug design, and genomics [1]. This review will describe progress in the field since the SAR by NMR (structure–activity relationship by nuclear magnetic resonance) approach using 2D 1H–15N HSQC spectra of 15N-labeled proteins was described by Fesik's group in 1996 [2]. Others have also written at length on NMR screening techniques [3], [4], [5], [6], [7], [8], [9], [10], [11]. The focus of this comprehensive review will be to first provide a physical and mathematical basis of the various NMR screening techniques and then to describe examples from the literature where the techniques have been applied to biological systems. Emphasis will be placed on applications in drug discovery and drug design. A discussion on NMR screening library design is also included, with particular emphasis on the elegant SHAPES library and its applications [12]. The review will conclude with sections on NMR screening's impact on chemistry and biology, prospects for automation and future directions.