Developments in electrospray ionization mass spectrometry of non-covalent DNA-ligand complexes
Many anti-cancer drugs function by binding non-covalently to double-stranded (ds) DNA. Electrospray ionization massspectrometry (ESI-MS) has emerged over the past decade as a sensitive technique for the determination of stoichiometriesand relative binding affinities of DNAligand interactions. The chromosome contains nucleotide sequences, for example,guanosine-rich regions, that predispose them to the formation of higher order structures such as quadruplexDNA(qDNA).Sequences that form qDNA are found in the telomeres. The proposal that ligands that stabilize qDNA might interfere withthe activity of telomerase in cancer cells has stimulated the search for ligands that are selective forqDNAover dsDNA. Theinsights gained from the development of ESI-MS methods for analysis of non-covalent dsDNAligand complexes are nowbeing applied in the search for qDNA-selective ligands. ESI-MS is a useful first-pass screening technique for qDNAbindingligands. This short review describes some experimental considerations for ESI-MS analysis of DNAligandcomplexes, briefly addresses the question of whether non-covalent DNAligand complexes are faithfully transferred fromsolution to the gas phase, discusses ion mobility mass spectrometry as a technique for probing this issue, and highlightssome recent ESI-MS studies of qDNA-selective ligands
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