Human Telomeric DNA Sequence-Specific Cleaving by G-Quadruplex Formation
Human Telomeric DNA Sequence-Specific Cleaving by G-Quadruplex Formation
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DOI：
10.1021/ja807313x
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发表时间：
2009-03-04
影响因子：
15
通讯作者：
Komiyama, Makoto
中科院分区：
文献类型：
--
作者：
Xu, Yan;Suzuki, Yuta;Komiyama, Makoto
端粒是治疗人类癌症的新兴靶点。在这里，我们报告了一种基于结构的方法，通过 G-四链体形成对人类端粒 DNA 进行序列特异性切割。 5' 端带有多磷酸盐 [DNA-EDTP-Ce(IV)] 的寡核苷酸通过形成 G-四链体与人端粒 DNA 结合，并导致序列特异性链断裂。这些结果为基于G-四链体形成靶向人类端粒DNA提供了第一个概念证明，这可以作为通过G-四链体形成设计更有效的端粒序列特异性切割试剂的起点。
Telomere is an emerging target for the treatment of human cancers. Here, we report a structure-based approach to sequence-specific cleaving of human telomeric DNA by G-quadruplex formation. Oligonucleotide with multiphosphonate [DNA-EDTP-Ce(IV)] at the 5' end binds to human telomere DNA by G-quadruplex formation and causes a sequence-specific strand break. These results provide the first proof of concept for targeting the human telomere DNA based on G-quadruplex formation, and this may serve as a starting point for the design of more efficient telomere sequence-specific cleaving reagents by G-quadruplex formation.