Applications of Nuclear Magnetic Resonance and Mass Spectrometry to Anticancer Drug Discovery

This chapter discusses the applications of nuclear magnetic resonance and mass spectrometry to anticancer drug discovery. Nuclear magnetic resonance (NMR) provides a plethora of tools that can be applied to address a number of issues or questions that typically occur during a drug development program. NMR is routinely used to determine high-resolution structures of proteins and protein-ligand complexes. Additionally, NMR can provide valuable information on the dynamic behavior of the same proteins and protein-ligand complexes. These data are essential to a structure-based drug discovery program. NMR has been used to address a fundamental issue associated with the drug discovery process, namely, to verify that a chemical lead actually binds in a biologically relevant manner to the protein target of interest. A variety of NMR techniques, including 2D heteronuclear single quantum coherence, saturation transfer difference, and 1D line-broadening, have been successfully applied to screening compound libraries by NMR. A variety of MS techniques have been used for structure elucidation, analysis of metabolism, diagnostics, and drug screening. It is found that the parallel development of MS as a technique to screen libraries for compounds that bind biomoleules and the complementary nature of NMR and MS lead to the development of the MS/NMR assay by combining the inherent strengths of these analytical techniques.