A minor groove binding copper-phenanthroline conjugate produces direct strand breaks via β-elimination of 2-deoxyribonolactone
A minor groove binding copper-phenanthroline conjugate produces direct strand breaks via β-elimination of 2-deoxyribonolactone
复制标题
DOI：
10.1021/ja026970z
复制
发表时间：
2002-08-07
影响因子：
15
通讯作者：
Greenberg, MM
中科院分区：
文献类型：
--
作者：
Bales, BC;Pitié, M;Greenberg, MM
铜-邻菲咯啉配合物及其偶联物是研究核酸相互作用的有用试剂。尽管20多年前就发现了这种复合物对DNA的切割，但关于DNA被破坏的化学机制的重要问题仍然没有答案。提供了动力学证据，表明与铜菲咯啉结合的小沟结合分子（6）导致DNA损伤的主要途径涉及C1 '-氧化。使用6和含有2-脱氧核糖内酯（1）的DNA底物进行的其他实验表明，直接链断裂是通过1的β-消除产生的。这些研究支持Sigman提出的铜邻菲咯啉对DNA损伤的原始机制和最近提出的关于直接链断裂形成机制的建议。
Copper-phenanthroline complexes and their conjugates are useful reagents for studying nucleic acid interactions. Although DNA cleavage by such complexes was discovered more than 20 years ago, significant questions remain unanswered regarding the chemical mechanism(s) by which DNA is damaged. Kinetic evidence is provided, which demonstrates that the major pathway for DNA damage by a minor groove binding molecule conjugated to copper phenanthroline (6) involves C1‘-oxidation. Additional experiments using6and a DNA substrate containing 2-deoxyribonolactone (1) show that direct strand breaks are produced via β-elimination from1. These studies support the original mechanism for DNA damage by copper phenanthroline put forth by Sigman and a more recent proposal concerning the mechanism for direct strand break formation.