Characterization of aziridinylbenzoquinone DNA cross-links by liquid chromatography-infrared multiphoton dissociation-mass spectrometry.
DNA cross-linking was evaluated by liquid chromatography-tandem mass spectrometry to determine the relative cross-linking abilities of two aziridinylbenzoquinones. Reactivities of RH1 (2,5-diaziridinyl-3-[hydroxymethyl]-6-methyl-1,4-benzoquinone), a clinically studied antitumor cross-linking agent, and an analogue containing a phenyl group (2,5-diaziridinyl-3-[hydroxymethyl]-6-phenyl-1,4-benzoquinone, PhRH1) rather than a methyl group were compared. The bulky phenyl substituent was added to determine the impact of steric hindrance on the formation of cross-links within a double helical structure. Cross-links formed by RH1 and PhRH1 were observed at 5'-dGNC sites as well as 5'-dGAAC/dGTTC sites. RH1 was more effective at forming cross-links than PhRH1 for a variety of duplexes. Infrared multiphoton dissociation (IRMPD) and collision-induced dissociation results confirmed the presence and the location of the cross-links within the duplexes, and IRMPD was used to identify the dissociation pathways of the cross-linked duplexes.
Pierce
Sarah E
SE
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, USA.
Guziec
Lynn J
LJ
Guziec
Frank S
FS
Brodbelt
Jennifer S
JS
D000970:Antineoplastic Agents / Q000737:chemistry*; D001388:Aziridines / Q000737:chemistry*; D016227:Benzoquinones / Q000737:chemistry*; D002853:Chromatography, Liquid; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
C117776:2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone; D000970:Antineoplastic Agents; D001388:Aziridines; D016227:Benzoquinones; D003432:Cross-Linking Reagents; D004247:DNA