The Leaving Group Strongly Affects H2O2-Induced DNA Cross-Linking by Arylboronates
The Leaving Group Strongly Affects H2O2-Induced DNA Cross-Linking by Arylboronates
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DOI：
10.1021/jo401901x
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发表时间：
2014-01-17
影响因子：
3.6
通讯作者：
Peng, Xiaohua
中科院分区：
文献类型：
--
作者：
Cao, Sheng;Wang, Yibin;Peng, Xiaohua
我们评估了苄基离去基团和芳基硼酸酯的核心结构对H2O2诱导形成的DNA链间交联的双醌甲基化物的影响。由这些芳基硼酸酯诱导的DNA交联的机制涉及苯酚中间体的产生，随后苄基离去基团的离开导致通过烷基化直接交联DNA的QM。QM形成是DNA交联的速率决定步骤。一个更好的离去基团（Br）和逐步双醌甲基化物的形成增加链间交联效率。这些发现为设计新的抗癌前药提供了必要的指导。
We evaluated the effects of the benzylic leaving group and core structure of arylboronates on H2O2-induced formation of bisquinone methides for DNA interstrand cross-linking. The mechanism of DNA cross-linking induced by these arylboronates involves generation of phenol intermediates followed by departure of benzylic leaving groups leading to QMs which directly cross-link DNA via alkylation. The QM formation is the rate-determining step for DNA cross-linking. A better leaving group (Br) and stepwise bisquinone methide formation increased interstrand cross-linking efficiency. These findings provide essential guidelines for designing novel anticancer prodrugs.