The Truncated Human Telomeric Sequence forms a Hybrid-Type Intramolecular Mixed Parallel/antiparallel G-quadruplex Structure in K+ Solution
The Truncated Human Telomeric Sequence forms a Hybrid-Type Intramolecular Mixed Parallel/antiparallel G-quadruplex Structure in K+ Solution
复制标题
截短的人端粒序列在 K 溶液中形成杂合型分子内混合平行/反平行 G-四链体结构
DOI：
10.1111/cbdd.12740
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发表时间：
2016
影响因子：
3
通讯作者：
Lin Weizhen
中科院分区：
文献类型：
--
作者：
Liu Yuxia;Cheng Dengfeng;Ge Min;Lin Weizhen
摘要在80-90%的肿瘤细胞中，端粒酶具有活性并稳定端粒的长度。端粒G-四链体的形成和稳定能抑制端粒酶的活性，因此端粒G-四链体已成为肿瘤治疗的潜在靶点。因此，K+溶液中形成的G-四链体的结构已成为研究的热点。然而，人类端粒G-四链体在K+中的确切结构存在极大的争议，本研究为了解不同的G-四链体提供了信息。在这里，我们报告，22 nt和24 nt的人类端粒序列形成单分子混合型混合平行/反平行G-四链体在K+溶液中阐明利用圆二色性，差示扫描量热法，和凝胶电泳。此外，这两个序列的个人配置推测在这项研究中。在生理条件下形成的G-四链体的详细结构信息对于基于结构的合理药物设计是必要的。
Abstract In 80-90% tumor cells, telomerase becomes active and stabilizes the length of telomeres. The formation and stabilization of G-quadruplexes formed from human telomeric sequences have been proved able to inhibit the activity of telomerase, thus human telomeric G-quadruplex structure has become a potential target for the development of cancer therapy. Hence, structure of G-quadruplex formed in K+solution has been an attractive hotspot for further studies. However, the exact structure of human telomeric G-quadruplex in K+is extremely controversial, this study provides information for the understanding of different G-quadruplexes. Here, we report that 22nt and 24nt human telomeric sequences form unimolecular hybrid-type mixed parallel/antiparallel G-quadruplex in K+solution elucidated utilizing Circular Dichroism, Differential Scanning Calorimetry, and gel electrophoresis. Moreover, individual configuration of these two sequences was speculated in this study. The detailed structure information of the G-quadruplex formed under physiologically relevant condition is necessary for structure-based rational drug design.