Evaluation of complexation of metal-mediated DNA-binding drugs to oligonucleotides via electrospray ionization mass spectrometry

AUTOR(ES)

Reyzer, Michelle L.

FONTE

Oxford University Press

RESUMO

The interactions of self-complementary oligonucleotides with a group of metal-mediated DNA-binding drugs, including chromomycin A3, mithramycin and the novel compound UK-1, were examined via electrospray ionization quadrupole ion trap mass spectrometry. Both chromomycin and mithramycin were shown to bind preferentially to GC-rich oligonucleotide duplexes in a 2:1 drug:metal ratio, while UK-1 was shown to bind in a 1:1 drug:metal stoichiometric ratio without a strong sequence preference. These trends were observed in the presence of Co2+, Ni2+ and Zn2+, with the exception that chromomycin–Zn2+ complexes were not readily observed. The binding stoichiometries as well as the sequence specificities are in agreement with literature reports for solution studies. Binding selectivities and stabilities of the complexes were also probed using electrospray ionization mass spectrometry. Both of the GC-rich oligomers 5′-GCGCGC-3′ and 5′-GCGCATGCGC-3′ exhibited a binding preference for chromomycin over mithramycin in the presence of Co2+ and Ni2+. Energy-variable collisionally activated dissociation of the complexes was employed to determine the stabilities of the complexes. The relative metal-dependent binding energies were Ni2+ > Zn2+ > Co2+ for UK-1–oligomer complexes and Ni2+ > Co2+ for both mithramycin and chromomycin complexes.

Documentos Relacionados

• Characterization of a multi-functional metal-mediated nuclease by MALDI-TOF mass spectrometry
• Bactericidal Activity of Metal-Mediated Peroxide-Ascorbate Systems
• Negative electrospray ionization mass spectrometry of synthetic and chemically modified oligonucleotides.
• Monitoring of β-blockers ozone degradation via electrospray ionization mass spectrometry
• Self-Organization of porphyrin-peptide units by metal-mediated peptide assembly