Ml. Reyzer et al., Evaluation of complexation of metal-mediated DNA-binding drugs to oligonucleotides via electrospray ionization mass spectrometry, NUCL ACID R, 29(21), 2001, pp. NIL_9-NIL_20
The interactions of self-complementary oligonucleotides with a group of met
al-mediated DNA-binding drugs, including chromomycin A(3), mithramycin and
the novel compound UK-1, were examined via electrospray ionization quadrupo
le ion trap mass spectrometry. Both chromomycin and mithramycin were shown
to bind preferentially to GC-rich oligonucleotide duplexes in a 2:1 drug:me
tal 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 t
he 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 we
re also probed using electrospray ionization mass spectrometry. Both of the
GC-rich oligomers 5'-GCGCGC-3' and 5'-GCGCATGCGC-3' exhibited a binding pr
eference 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 comple
xes and Ni2+ > Co2+ for both mithramycin and chromomycin complexes.