• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Anti-Cancer Drug Design >Role of DNA minor groove alkylation and DNA cross-linking in the cytotoxicity of polybenzamide mustards.
【24h】

Role of DNA minor groove alkylation and DNA cross-linking in the cytotoxicity of polybenzamide mustards.

机译：DNA小沟烷基化和DNA交联在聚苯甲酰胺芥菜的细胞毒性中的作用。

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

Interstrand DNA cross-links have been considered essential to the activity of current clinical DNA-alkylating antitumour drugs, which generally alkylate in the major groove. However, the relationship between cross-linking adducts located in the minor groove of DNA with cytotoxicity and antitumour activity has not been extensively investigated. Previous studies have shown that cross-linking ability is not correlated with cytotoxicity in a novel series of polybenzamide-linked nitrogen mustard compounds which alkylate DNA at adenines in the minor groove. In the present study the nature of these cross-linking adducts was explored for a related pair of compounds which are both highly effective cross-linkers but which differ in antitumour potential. Both of these drugs effectively interact with adenines in the minor groove, although their sequence specificity differs. However, the cross-linking event was not inhibited by pre-treatment with Hoechst 33258, although this pre-treatment effectively prevented adenine alkylation. The primary cross-links detected may thus represent guanine N7 alkylations in the major groove. Whether minor groove cross-linking adducts can be formed is uncertain, since the effect of background guanine N7 alkylation may complicate analysis. The cytotoxicity of the polybenzamides may therefore be related to other factors such as their interaction with cellular repair systems.
机译：链间DNA交联被认为是目前临床上DNA烷基化抗肿瘤药的活性必不可少的，这些药物通常在大沟中烷基化。然而，尚未广泛研究位于DNA小沟中的交联加合物与细胞毒性和抗肿瘤活性之间的关系。先前的研究表明，在一系列新的聚苯甲酰胺连接的氮芥化合物中，交联能力与细胞毒性不相关，该化合物使小沟中腺嘌呤的DNA烷基化。在本研究中，针对相关化合物对探索了这些交联加合物的性质，这对化合物都是高效交联剂，但抗肿瘤潜力不同。尽管它们的序列特异性不同，但这两种药物都可以有效地与小沟中的腺嘌呤相互作用。然而，尽管用Hoechst 33258进行预处理可以有效地防止腺嘌呤烷基化，但是交联事件并未受到其抑制。因此，检测到的主要交联可以代表主要凹槽中的鸟嘌呤N7烷基化。由于背景鸟嘌呤N7烷基化的影响可能使分析复杂化，因此能否形成次要的沟槽交联加合物尚不确定。因此，聚苯甲酰胺的细胞毒性可能与其他因素有关，例如它们与细胞修复系统的相互作用。

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