Liu Yuxia, Cheng Dengfeng, Ge Min, Lin Weizhen
Center for Thorium Molten Salt Reactor System, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 2019 Jialuo Road, Shanghai, 201800, China.
Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
Chem Biol Drug Des. 2016 Jul;88(1):122-8. doi: 10.1111/cbdd.12740. Epub 2016 Mar 9.
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.
在80%-90%的肿瘤细胞中，端粒酶变得活跃并稳定端粒的长度。由人类端粒序列形成的G-四链体的形成和稳定已被证明能够抑制端粒酶的活性，因此人类端粒G-四链体结构已成为癌症治疗开发的潜在靶点。因此，在钾离子溶液中形成的G-四链体结构一直是进一步研究的一个有吸引力的热点。然而，钾离子溶液中人类端粒G-四链体的确切结构极具争议，本研究为理解不同的G-四链体提供了信息。在此，我们报告利用圆二色性、差示扫描量热法和凝胶电泳阐明，22nt和24nt人类端粒序列在钾离子溶液中形成单分子杂合型混合平行/反平行G-四链体。此外，本研究推测了这两个序列的个体构型。在生理相关条件下形成的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。
