Evaluation of the selectivity of G-quadruplex ligands in living cells with a small molecule fluorescent probe.
Evaluation of the selectivity of G-quadruplex ligands in living cells with a small molecule fluorescent probe.
复制标题
用小分子荧光探针评估活细胞中 G-四链体配体的选择性
DOI：
10.1016/j.acax.2019.100017
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发表时间：
2019-07
影响因子：
--
通讯作者：
Tang Y
中科院分区：
文献类型：
--
作者：
Zhang S;Sun H;Yang D;Liu Y;Zhang X;Chen H;Li Q;Guan A;Tang Y
由于G-四链体在肿瘤学中的重要生理作用，其已成为药物设计的新兴靶点。在过去的几十年里，合成和药物化学家已经开发了许多四链体相互作用的配体。然而，巨大的挑战仍然存在，用于检测这些配体对细胞中的G-四链体结构的特异性靶向的方法仍然缺乏。本文中，通过使用小分子荧光探针（IMT）作为荧光指示剂，构建了用于直接鉴定细胞中配体对DNA G-四链体的特异性靶向的检测系统。四个典型的配体已成功地进行了评估，表明该检测系统在四链体特异性治疗药物的筛选和评估中有着广阔的应用前景。报道了一种有效的用于评估G-四链体配体在活细胞中的靶向的系统。成功地确定了四种典型配体在活细胞中对G-四链体的靶向作用。该检测系统在四重靶向药物的筛选和评价中显示出良好的应用前景。
G-quadruplex has been an emerging target for drug design due to its physiologically important roles in oncology. A number of quadruplex-interactive ligands have been developed by synthetic and medicinal chemists over the past decades. However, the great challenge still remains that the method for detecting the specific targeting of these ligands to the G-quadruplex structures in cells is still lacking. Herein, a detection system for directly identifying the specific targeting of a ligand to DNA G-quadruplexes in cells was constructed by using a small-molecular fluorescent probe (IMT) as a fluorescent indicator. Four typical ligands have been successfully evaluated, demonstrating the promising application of this detection system in the screening and evaluation of quadruplex-specific therapeutic agents. An effective system for assessing the targeting of G-quadruplex ligands in living cells is reported. The targeting of four typical ligands to G-quadruplexes in live cells was successfully determined. This detection system shows promising applications in the screening and evaluation of quadruplex-targeted drugs.