School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore.
Biophys J. 2011 Oct 19;101(8):1987-98. doi: 10.1016/j.bpj.2011.08.049.
Understanding the fundamentals of G-quadruplex formation is important both for targeting G-quadruplexes formed by natural sequences and for engineering new G-quadruplexes with desired properties. Using a combination of experimental and computational techniques, we have investigated the effects of site-specific substitution of a guanine with C8-modified guanine derivatives, including 8-bromo-guanine, 8-O-methyl-guanine, 8-amino-guanine, and 8-oxo-guanine, within a well-defined (3 + 1) human telomeric G-quadruplex platform. The effects of substitutions on the stability of the G-quadruplex were found to depend on the type and position of the modification among different guanines in the structure. An interesting modification-dependent NMR chemical-shift effect was observed across basepairing within a guanine tetrad. This effect was reproduced by ab initio quantum mechanical computations, which showed that the observed variation in imino proton chemical shift is largely influenced by changes in hydrogen-bond geometry within the guanine tetrad.
了解 G-四链体形成的基本原理对于靶向天然序列形成的 G-四链体以及工程设计具有预期性质的新 G-四链体都很重要。我们采用实验和计算技术相结合的方法,研究了在明确的(3 + 1)人类端粒 G-四链体平台中,特定位置的碱基替换对 G-四链体稳定性的影响。取代对 G-四链体稳定性的影响取决于结构中不同碱基上修饰的类型和位置。在鸟嘌呤四联体内部的碱基配对中观察到有趣的与修饰相关的 NMR 化学位移效应。该效应通过从头算量子力学计算得到了重现,表明观察到的亚氨基质子化学位移的变化在很大程度上受到鸟嘌呤四联体内部氢键几何形状变化的影响。