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

Citation
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
Citations number
35
Categorie Soggetti
Biochemistry & Biophysics
Journal title
NUCLEIC ACIDS RESEARCH
ISSN journal
03051048 → ACNP
Volume
29
Issue
21
Year of publication
2001
Pages
NIL_9 - NIL_20
Database
ISI
SICI code
0305-1048(20011101)29:21<NIL_9:EOCOMD>2.0.ZU;2-C
Abstract
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.