Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry

Abstract

dpqC]Cl 2 with DNA, highlighting the need for obtaining ESI mass spectra of non-covalent complexes under a range of experimental conditions. Negative ion spectra of mixtures of the minor groove binder Hoechst 33258 with DNA containing a known minor groove binding sequence were dominated by ions from a 1:1 complex. In contrast, in positive ion spectra there were also ions present from a 2:1 (Hoechst 33258: DNA) complex, suggesting an alternative binding mode was possible either in solution or in the gas phase. When Hoechst 33258 was mixed with a DNA sequence lacking a high affinity minor groove binding site, the negative ion ESI mass spectra showed that 1:1 and 2:1 complexes were formed, consistent with existence of binding modes other than minor groove binding. The data presented suggest that comparison of positive and negative ion ESI-MS spectra might provide an insight into various binding modes in both solution and the gas phase. (J Am Soc Mass Spectrom 2004, 15, 1382-1391

Positive and negative ion mode ESI-MS and MS/MS for studying drug–DNA complexes

“…All results presented here demonstrate that there are neither false positives, nor false negatives in the complexes observed in negative ion mode ESI-MS. In positive ion mode, there may be some false negatives, as has been shown by Sheil and coworkers [20,21] and in the present work for the intercalators that bind to duplex DNA exclusively by stacking interactions. At the most, positive ion mode could be used, when a complex is detected in negative ion mode, to test whether the complex involved purely stacking interactions or whether there are other hydrogen bonding interactions remaining.…”

“…Several papers demonstrated that this approach gives reliable apparent binding constants in the case of duplex DNA [15,16], quadruplex DNA [17], and different RNA structures [18,19]. Some papers were recently published on ESI mass spectra of DNA acquired using positive ion mode [20,21]. We therefore wanted to assess whether the positive ion spectra are likely to provide an accurate picture of the drug-DNA complexes present in solution.…”

Evaluation of DNA/Ligand Interactions by Electrospray Ionization Mass Spectrometry

“…Overall, the DNA-binding affinities of the APs obtained by ESI-MS screening correlated with their inhibitory activities. ESI-MS has also been used to evaluate the complexation of other types of novel ligands (28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40), including acridines (31), cationic porphyrins (36), cryptolepine alkaloids (37), protoberbine alkaloids (38), benzopyridoindole and benzopyridoquinoxaline compounds (32), and acridine-and naphthalene-derived macrocyclic bis-intercalators (33), with DNA duplexes.…”

Screening of threading bis-intercalators binding to duplex DNA by electrospray ionization tandem mass spectrometry

“…There have been numerous ESI-MS studies that have examined the interaction between duplex DNA and well-studied, commercially available mono-intercalators such as the anthracyclines [6][7][8][9][10][11], porphyrins [12,13], ruthenium compounds [11][12][13][14][15], ethidium bromide [16][17][18], actinomycin-D [12,13], and aureolic acids [19]. Characteristics such as ligand binding stoichiometry [7,8,[11][12][13][14]16], sequence selectivity [7,11,13,14,16,19], binding mode [12,13,15] and complex stability [9,12,16] have been examined with promising results correlating the binding trends observed in the mass spectra to known solution behavior. While the binding of many commercial monointercalators has been well-studied by ESI-MS, there has been only one study [20] that has focused on a bisintercalator, ditercalinium.…”