Existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy.

Existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy.
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G-四链体 DNA 交联策略证实癌基因启动子区存在 G-四链体结构

DOI:
10.1038/srep01811
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发表时间:
2013
期刊:
影响因子:
4.6
通讯作者:
Zhou, Xiang
Zhou, Xiang
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yuan, Libo;Tian, Tian;Chen, Yuqi;Yan, Shengyong;Xing, Xiwen;Zhang, Zhengan;Zhai, Qianqian;Xu, Liang;Wang, Shaoru;Weng, Xiaocheng;Yuan, Bifeng;Feng, Yuqi;Zhou, Xiang

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G-四链体DNA在体内的存在一直是生物学和生物化学领域的研究热点。本文报道了用G-四链体DNA交联法证实癌基因启动子区存在G-四链体结构的结果。设计并合成了对G-四链体交联具有高选择性的G-四链体交联探针。进一步的生物学研究表明其对小鼠黑色素瘤细胞具有良好的抑制活性。为了进一步研究G-四链体DNA是否在体内形成并作为靶标,合成了衍生物,并结合圆二色性和高通量深度测序进行了染色体DNA的下拉过程。几种模拟细胞内条件,包括X。Iaevis卵母细胞,Ficoll 70和PEG,用于研究化合物对预形成的G-四链体的纯交联能力。因此,作为一种有效的G-四链体交联剂,我们的策略既提供了体内G-四链体结构的有价值的证据,又提供了在抗癌治疗中的巨大潜力。
Existence of G-quadruplex DNA in vivo always attract widespread interest in the field of biology and biological chemistry. We reported our findings for the existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy. Probes for selective G-quadruplex cross-linking was designed and synthesized that show high selectivity for G-quadruplex cross-linking. Further biological studies demonstrated its good inhibition activity against murine melanoma cells. To further investigate if G-quadruplex DNA was formed in vivo and as the target, a derivative was synthesized and pull-down process toward chromosome DNAs combined with circular dichroism and high throughput deep sequencing were performed. Several simulated intracellular conditions, including X. laevis oocytes, Ficoll 70 and PEG, was used to investigate the compound's pure cross-linking ability upon preformed G-quadruplex. Thus, as a potent G-quadruplex cross-linking agent, our strategy provided both valuable evidence of G-quadruplex structures in vivo and intense potential in anti-cancer therapy.
DOI: 10.1093/nar/gkr174
发表时间: 2011-07
影响因子: 14.9
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影响因子: 11.1
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