...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >Conformations of adducts formed between the genotoxic benzo[a]pyrene-7,8-dione and nucleosides studied by density functional theory
【24h】

Conformations of adducts formed between the genotoxic benzo[a]pyrene-7,8-dione and nucleosides studied by density functional theory

机译：用密度泛函理论研究遗传毒性苯并[a] py-7,8-二酮与核苷之间形成的加合物构象

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

Benzo[a]pyrene (BP) is a widely distributed environmental pollutant that is metabolized by mammalian cells to a variety of genotoxic and carcinogenic intermediates that form covalent adducts with cellular DNA. One such pathway involves the metabolic activation of BP by members of the aldo-keto-reductase (AKR) family of enzymes to the highly reactive ortho-quirione, benzo[a]pyrene-7,8-dione (BPQ). This compound has been reported to react with the 2'-deoxynucleosides, dA and dG, under physiological conditions. Four BPQ-dG adducts and two -dA adducts were identified by mass spectrometry and NMR methods [Balu et al. (2004) Chem. Res. Toxicol. 17, 827-838]. However, the detailed conformations and absolute configurations around the linkage site have not been resolved. In order to determine the full conformations of these purine adducts, we carried out quantum mechanical geometry optimization using density functional theory. In the case of the BPQ-guanine adducts, six possible structures, each of which consists of two isomers, were identified. However, in the case of the adenine adducts, only four isomers were identified. The results suggest that stereoisomeric adduct pairs are expected to adopt opposite orientations with respect to the 5'-> 3' direction of the modified DNA strands. The stereochemistry-dependent variations in adduct orientation may produce different biological effects, as has been observed in the case of DNA adducts derived from other metabolites of polycyclic aromatic hydrocarbons. (c) 2006 Elsevier B.V All rights reserved.
机译：苯并[a] py（BP）是一种分布广泛的环境污染物，被哺乳动物细胞代谢为多种遗传毒性和致癌性中间体，与细胞DNA形成共价加合物。一种这样的途径涉及通过醛基酮还原酶（AKR）家族的成员对高反应性邻基奎酮，苯并[a] py-7,8-二酮（BPQ）的代谢代谢。据报道，该化合物在生理条件下可与2'-脱氧核苷dA和dG反应。通过质谱和NMR方法鉴定了四个BPQ-dG加合物和两个-dA加合物[Balu et al.。 （2004）Chem。 Res。毒药。 17，827-838]。但是，尚未解决链接站点周围的详细构象和绝对配置。为了确定这些嘌呤加合物的完整构象，我们使用密度泛函理论进行了量子力学几何优化。对于BPQ-鸟嘌呤加合物，鉴定了六个可能的结构，每个结构均由两个异构体组成。然而，对于腺嘌呤加合物，仅鉴定出四个异构体。结果表明，预期立体异构加合物对相对于修饰的DNA链的5'-> 3'方向采用相反的取向。加合物取向的立体化学依赖性变化可能产生不同的生物学效应，正如在衍生自多环芳烃其他代谢产物的DNA加合物的情况下所观察到的那样。 （c）2006 Elsevier B.V保留所有权利。

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