• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of mass spectrometry: JMS >Structures of oxaliplatin-oligonucleotide adducts from DNA
【24h】

Structures of oxaliplatin-oligonucleotide adducts from DNA

机译：DNA的奥沙利铂-寡核苷酸加合物的结构

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Oxaliplatin, [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O') platinum(II) shows a great efficiency against colorectal cancer. Although the mode of action of oxaliplatin is not yet understood, it is commonly accepted that binding of oxaliplatin to DNA prevents DNA synthesis and alters protein to DNA binding. In order to elucidate the modified DNA-protein interaction and thus to understand the mechanisms leading to cellular misinterpretation of DNA information and apoptosis, we have identified the preferential binding sites and the dynamics of the oxaliplatin-DNA intrastrand and interstrand adducts at the oligomer level using high-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS) and HPLC/inductively coupled plasma-MS for quantitative studies. We used a combination of benzonase, alkaline phosphatase and Nuclease S1 for digestion. This digestion procedure allows the study of platinated oligomeric nucleotides and more complex interstrand adducts. The digestion products were mostly chromatographically separated and characterized using HPLC/ESI-ion trap MS/MS experiments. We could show that the adducts to guanine and adenine are quite dynamic; that is, the ratios are changing for several days. In addition, the resulting adducts provide evidence for the action of the digesting enzymes and indicate that the adduct spectrum at the oligomeric level is different to that at the commonly studies dinucleotide level.
机译：奥沙利铂，[（1R，2R）-环己烷-1,2-二胺]（乙二酰-O，O'）铂（II）对结直肠癌的治疗效果显着。尽管尚不了解奥沙利铂的作用方式，但普遍认为奥沙利铂与DNA的结合会阻止DNA的合成并改变蛋白质与DNA的结合。为了阐明修饰的DNA与蛋白质的相互作用，从而了解导致细胞对DNA信息的错误解释和凋亡的机制，我们使用低聚物水平鉴定了奥沙利铂-DNA链内和链间加合物的优先结合位点和动力学，方法是使用高效液相色谱/电喷雾串联质谱法（HPLC / ESI-MS / MS）和HPLC /电感耦合等离子体质谱法进行定量研究。我们使用了苯甲酸酶，碱性磷酸酶和核酸酶S1的组合进行消化。该消化程序允许研究铂化的寡聚核苷酸和更复杂的链间加合物。消化产物大部分经色谱分离，并使用HPLC / ESI离子阱MS / MS实验进行表征。我们可以证明鸟嘌呤和腺嘌呤的加合物是动态的。也就是说，比率会连续几天变化。此外，所得的加合物为消化酶的作用提供了证据，并表明在寡聚体水平上的加合物谱不同于通常研究的二核苷酸水平上的加合物谱。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号