DNA Recognition by a Novel Bis-Intercalator, Potent Anticancer Drug XR5944.
DNA Recognition by a Novel Bis-Intercalator, Potent Anticancer Drug XR5944.
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DOI：
10.2174/1568026615666150413155608
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发表时间：
2015
影响因子：
3.4
通讯作者：
Yang D
中科院分区：
文献类型：
--
作者：
Lin C;Yang D
XR5944是一种有效的抗癌药物，具有一种新的DNA结合模式：DNA双插层与主槽结合。XR5944可以结合雌激素反应元件（estrogen response element， ERE）序列，阻断ER-ERE结合，抑制ERα活性，这可能有助于克服现有抗雌激素治疗的耐药性。本文就XR5944特异性DNA识别的结构和功能研究进展作一综述。天然启动子序列内的嵌入位点似乎与理想的结合位点不同，并且依赖于上下文和序列。这些结构信息可以为合理设计改进的ere特异性XR5944衍生物以及一般的DNA双插层器提供见解。
XR5944 is a potent anticancer drug with a novel DNA binding mode: DNA bis-intercalationg with major groove binding. XR5944 can bind the estrogen response element (ERE) sequence to block ER-ERE binding and inhibit ERα activities, which may be useful for overcoming drug resistance to currently available antiestrogen treatments. This review discusses the progress relating to the structure and function studies of specific DNA recognition of XR5944. The sites of intercalation within a native promoter sequence appear to be different from the ideal binding site and are context- and sequence- dependent. The structural information may provide insights for rational design of improved ERE-specific XR5944 derivatives, as well as of DNA bis-intercalators in general.