Interaction between antitumor drugs and a double-stranded oligonucleotide studied by electrospray ionization mass spectrometry

✍ Scribed by Gabelica, Valérie; De Pauw, Edwin; Rosu, Frédéric

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 198 KB
• Volume: 34
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/(sici)1096-9888(199912)34:12<1328::aid-jms889>3.0.co;2-f

✦ Synopsis

Electrospray ionization mass spectrometry was used to investigate the complex formation between a doublestranded oligonucleotide and various antitumor drugs belonging to two categories: intercalators (ethidium bromide, amsacrine and ascididemin) and minor groove binders (Hoechst 33258, netropsin, distamycin A, berenil and DAPI). The goal of this study was to determine whether the relative intensities in the mass spectra reflect the relative abundances of the species in the solution phase. The full-scan mass spectra suggest non-specific binding for the intercalators and specific binding for the minor groove binders. The preferential stoichiometries adopted by each minor groove binder were determined by studying the influence of the drug concentration on the spectra. We obtained 2 : 1 > 1 : 1 for distamycin, 1 : 1 > 2 : 1 for Hoechst 33258 and DAPI and only the 1 : 1 complex for netropsin and berenil. These features reflect their known behavior in solution. The compared tandem mass spectra of the 1 : 1 complexes with Hoechst 33258 and netropsin, when correlated with published crystallographic data, suggest the possibility of inferring some structural information. The relative binding affinities of the drug for the considered duplex were deduced with two by two competition experiments, assuming that the relative intensities reflect the composition of the solution phase. The obtained affinity scale is netropsin > distamycin A > DAPI > Hoechst 33258 > berenil. These examples show some of the potential uses of mass spectrometry as a useful tool for the characterization of specific drug binding to DNA, and possibly a rapid drug screening method requiring small amounts of materials.