用液相色谱-红外多光子解离-质谱法对氮丙啶基苯醌 DNA 交联物进行表征。
Characterization of aziridinylbenzoquinone DNA cross-links by liquid chromatography-infrared multiphoton dissociation-mass spectrometry.
机构信息
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, USA.
出版信息
Chem Res Toxicol. 2010 Jun 21;23(6):1097-104. doi: 10.1021/tx1000738.
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.
DNA 交联作用通过液相色谱-串联质谱法进行评估，以确定两种氮丙啶基苯醌的相对交联能力。比较了临床研究的抗肿瘤交联剂 RH1（2,5-二氮丙啶基-3-[羟甲基]-6-甲基-1,4-苯醌）及其类似物的反应性，类似物中含有苯环（2,5-二氮丙啶基-3-[羟甲基]-6-苯基-1,4-苯醌，PhRH1）而不是甲基。添加大体积的苯基取代基是为了确定空间位阻对双螺旋结构中形成交联的影响。RH1 和 PhRH1 在 5'-dGNC 位点以及 5'-dGAAC/dGTTC 位点形成交联。与 PhRH1 相比，RH1 更有效地形成各种双链体的交联。红外多光子解离（IRMPD）和碰撞诱导解离结果证实了交联在双链体中的存在和位置，并且使用 IRMPD 来鉴定交联双链体的解离途径。
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