Comparison of the binding stoichiometries of positively charged DNA-binding drugs using positive and negative ion electrospray ionization mass spectrometry.
Positive and negative ion electrospray ionization (ESI) mass spectra of complexes of positively charged small molecules (distamycin, Hoechst 33258, [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2) have been compared. [Ru(phen)2dpq]Cl2 and [Ru(phen)2dpqC]Cl2 bind to DNA by intercalation. Negative ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 with DNA showed ions from DNA-ligand complexes consistent with solution studies. In contrast, only ions from free DNA were present in positive ion ESI mass spectra of mixtures of [Ru(phen)2dpq]Cl2 or [Ru(phen)2dpqC]Cl2 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.
Gupta
Rajesh
R
Department of Chemistry and Vice-Chancellors Unit, University of Wollongong, Northfields Avenue, 2522, Wollongong, New South Wales, Australia.
Beck
Jennifer L
JL
Department of Chemistry and Vice-Chancellors Unit, University of Wollongong, Northfields Avenue, 2522, Wollongong, New South Wales, Australia.
Ralph
Stephen F
SF
Department of Chemistry and Vice-Chancellors Unit, University of Wollongong, Northfields Avenue, 2522, Wollongong, New South Wales, Australia.
Sheil
Margaret M
MM
Department of Chemistry and Vice-Chancellors Unit, University of Wollongong, Northfields Avenue, 2522, Wollongong, New South Wales, Australia. msheil@uow.edu.au.
Aldrich-Wright
Janice R
JR
School of Science, Food and Horticulture, Campbelltown Campus, University of Western Sydney, New South Wales, Australia.
D006690:Bisbenzimidazole / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004214:Distamycins / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D055672:Static Electricity
D004214:Distamycins; D007364:Intercalating Agents; D004364:Pharmaceutical Preparations; D012428:Ruthenium; C030000:stallimycin; D004247:DNA; D006690:Bisbenzimidazole