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.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)