Mathad Raveendra I, Yang Danzhou
Department of Chemistry, BIO5 Institute, College of Pharmacy, The University of Arizona, Tucson, AZ, USA.
Methods Mol Biol. 2011;735:77-96. doi: 10.1007/978-1-61779-092-8_8.
G-quadruplexes are noncanonical secondary structures formed in DNA sequences containing consecutive runs of guanines. DNA G-quadruplexes have recently emerged as attractive cancer therapeutic targets. It has been shown that the 3' G-rich single-stranded overhangs of human telomeres can form G-quadruplex structures. G-quadruplex-interactive compounds have been shown to inhibit telomerase access as well as telomere capping. Nuclear magnetic resonance (NMR) spectroscopy has been shown to be a powerful method in determining the G-quadruplex structures under physiologically relevant conditions. We present the NMR methodology used in our research group for structure determination of G-quadruplexes in solution and their interactions with small molecule compounds. An example of a G-quadruplex structure formed in the human telomere sequence recently solved in our laboratory is used as an example.
G-四链体是在含有连续鸟嘌呤链的DNA序列中形成的非经典二级结构。DNA G-四链体最近已成为有吸引力的癌症治疗靶点。研究表明,人类端粒的3'富含鸟嘌呤的单链突出端可形成G-四链体结构。G-四链体相互作用化合物已被证明可抑制端粒酶的接近以及端粒封端。核磁共振(NMR)光谱已被证明是在生理相关条件下确定G-四链体结构的有力方法。我们介绍了我们研究小组用于溶液中G-四链体结构测定及其与小分子化合物相互作用的NMR方法。以我们实验室最近解析的人类端粒序列中形成的G-四链体结构为例。