Gee J E, Revankar G R, Rao T S, Hogan M E
Center for Biotechnology, Baylor College of Medicine, Woodlands, Texas 77381.
Biochemistry. 1995 Feb 14;34(6):2042-8. doi: 10.1021/bi00006a026.
Triplex-forming oligodeoxyribonucleotides (TFOs) can be designed so as to form antiparallel triple helices with duplex DNA by means of GGC and TAT or AAT base triplets, and these have been shown to be useful as sequence-specific DNA binding agents. Using TFOs targeted to the promoter region of the rat neu oncogene, it is shown here that substitution of an imidazole-nucleoside chimera at a single site in a neu specific TFO results in an increase in TFO binding affinity and specificity. This effect is discussed in terms of the stabilizing effect of local imidazole-TA triplet formation. It is also found that site-selective substitution of 2'-deoxy-6-thioguanosine for guanosine (S6-dG) in the TFO results in an increase in triplex formation in the presence of physiological levels of potassium ion. The utility and positioning of S6-dG base substitutions is discussed in the context of an intramolecular tetrad model.
三链形成寡脱氧核糖核苷酸（TFOs）可以通过GGC和TAT或AAT碱基三联体设计成与双链DNA形成反平行三链螺旋，并且这些已被证明可作为序列特异性DNA结合剂。利用靶向大鼠neu癌基因启动子区域的TFOs，本文表明在neu特异性TFO的单个位点处用咪唑核苷嵌合体进行取代会导致TFO结合亲和力和特异性增加。根据局部咪唑-TA三联体形成的稳定作用来讨论这种效应。还发现，在TFO中用2'-脱氧-6-硫代鸟苷（S6-dG）对鸟苷进行位点选择性取代会在生理水平的钾离子存在下导致三链形成增加。在分子内四联体模型的背景下讨论了S6-dG碱基取代的效用和定位。
