title: Interactions of mitoxantrone with duplex and triplex DNA studied by electrospray ionization mass spectrometry.
abstract: We have examined interactions between mitoxantrone (MXT) and DNA duplexes or triplexes with different base compositions by using electrospray ionization mass spectrometry (ESI-MS), respectively. MXT interacts preferentially with DNA duplexes compared to the triplexes. In the mass spectrum of the duplex-MXT mixture, the complex peaks dominated in the ratios of duplex/MXT of 1:1, 1:2 and 1:3, and the 1:2 duplex/MXT peak was the most abundant. In contrast, only 1:1 triplex-MXT complexes were observed in the mass spectrum of the triplex-MXT mixture, and the most intensive peak was a free triplex ion without MXT. Moreover, no sequence selectivity of MXT to different DNA duplexes was found while MXT showed greater affinity to the triplexes that have adjacent TAT or C(+)GC sequences. In the course of sustained off-resonance irradiation collision-induced dissociation (SORI-CID), the MXT-duplex complexes generated two separated strands, and the MXT remained on the purine strand side. UV/Vis spectra showed that MXT interacted with DNA by intercalation. Compared with emodin (a duplex intercalator) and napthylquinoline (a triplex binder), we found that the side chain of MXT might play a role in the binding of MXT to the duplexes and the triplexes. ESI-MS shows an advantage in speed and straightforwardness for the study of drug interactions with nucleic acids.
authors.affiliation: Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, PR China.
authors.forename: Cuihong
authors.initials: C
authors.lastname: Wan
authors.forename: Xinhua
authors.initials: X
authors.lastname: Guo
authors.forename: Fengrui
authors.initials: F
authors.lastname: Song
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.forename: Shuying
authors.initials: S
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004642:Emodin / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry; D008942:Mitoxantrone / Q000737:chemistry*; D009690:Nucleic Acid Conformation; D011804:Quinolines / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D007364:Intercalating Agents; D011804:Quinolines; C051802:triplex DNA; D004247:DNA; D008942:Mitoxantrone; D004642:Emodin