Evaluation of DNA/Ligand Interactions by Electrospray Ionization Mass Spectrometry

Electrospray ionization mass spectrometry (ESI-MS) has enabled the detection and characterization of DNA/ligand complexes, including evaluation of both relative binding affinities and selectivities of DNA-interactive ligands. The noncovalent complexes that are transferred from the solution to the gas phase retain the signature of the native species, thus allowing the use of MS to screen DNA/ligand complexes, reveal the stoichiometries of the complexes, and provide insight into the nature of the interactions. Ligands that bind to DNA via metal-mediated modes and those that bind to unusual DNA structures, such as quadruplexes, are amenable to EST. Chemical probe methods applied to DNA/ligand complexes with ESI-MS detection afford information about ligand-binding sites and conformational changes of DNA that occur upon ligand binding.