ABSTRACT
Shortly after the development of electrospray ionization mass spectrometry (ESI-MS),1-3 it was reported that this method could be used to detect intact noncovalent complexes.1-4 Since this seminal report in 1991, the literature concerning supramolecular complex analysis by ESI-MS has been
constantly growing. The complexes studied to date include from synthetic assemblies (cation-macrocycle, supramolecular assemblies, etc.) to complexes of biochemical interest (protein-protein, protein-ligand, protein-DNA, protein-RNA associations, etc.), and this list is not exhaustive.5-9 The ESI-MS of noncovalent complexes has now found important applications as a screening tool in drug discovery,10-14 including for DNA-or RNA-targeting drugs.10-14
This chapter focuses on the uses of ESI-MS for the study of noncovalent complexes between nucleic acids and small molecule ligands. Two reviews appeared on the subject in 2001, and another in 2008; useful information on drug-nucleic acid interaction studies can also be found in more general reviews.12,15-20 The ionization sources, other than electrospray, that have been successfully used to detect DNA duplexes and higher-order structures, or nucleic acid-ligand noncovalent complexes, are matrix-assisted laser desorption/ionization (MALDI), cold-spray ionization (CSI), laser spray ionization (LSI), and laser-induced liquid beam ion desorption (LILBID).21-27 These methods and their results will not be discussed in this chapter, but most of the general principles described here also hold for these other ionization methods.
