Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
J Am Chem Soc. 2009 Mar 4;131(8):2871-4. doi: 10.1021/ja807313x.
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.
端粒是人类癌症治疗的一个新兴靶点。在这里，我们报告了一种基于结构的方法，通过形成 G-四链体来特异性切割人类端粒 DNA。5'端带有多膦酸酯的寡核苷酸[DNA-EDTP.Ce(IV)]通过 G-四链体形成与人类端粒 DNA 结合，并导致序列特异性的链断裂。这些结果为基于 G-四链体形成靶向人类端粒 DNA 提供了第一个概念验证，并且这可能成为通过 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。
