College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei, 430072, P R China.
Sci Rep. 2013;3:1811. doi: 10.1038/srep01811.
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.
体内 G-四链体 DNA 的存在一直吸引着生物学和生物化学领域的广泛关注。我们通过 G-四链体 DNA 交联策略报告了在癌基因启动子区存在 G-四链体结构的发现。设计并合成了用于选择性 G-四链体交联的探针，其对 G-四链体交联具有很高的选择性。进一步的生物学研究表明，它对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点，合成了一种衍生物，并进行了与染色体 DNA 的下拉过程，结合圆二色性和高通量深度测序进行了研究。使用了几种模拟的细胞内条件，包括非洲爪蟾卵母细胞、Ficoll 70 和 PEG，以研究化合物在预形成的 G-四链体上的纯交联能力。因此，作为一种有效的 G-四链体交联剂，我们的策略为体内 G-四链体结构提供了有价值的证据，并在抗癌治疗方面具有巨大的潜力。
