Chandler S P, Strekowski L, Wilson W D, Fox K R
Department of Physiology and Pharmacology, University of Southampton, U.K.
Biochemistry. 1995 May 30;34(21):7234-42. doi: 10.1021/bi00021a039.
We have examined the effect of four triplex-binding ligands on the interaction of the oligodeoxynucleotides T8NT8 (N = A, G, C, T) with DNA fragments containing the sequences A8XA8.T8YT8 (X = G, C, T; Y = C, G, A) by DNase I footprinting. The ligands form a series of quinoline derivatives with an alkylamine chain in the 4-position and different aryl substituents in the 2-position. By themselves these compounds do not alter DNase I digestion of the DNA duplexes at concentrations up to 100 microM. At a concentration of 10 microM they potentiate triplex formation, lowering the concentration of oligonucleotide required to produce a clear footprint by as much as 100-fold. As well as stabilizing triplexes which consist of well-characterized DNA triplets, they also promote the formation of complexes which contain central triplet mismatches. This reduction in the stringency of triple helix formation may be used to broaden the range of triplex target sequences and enable recognition at sites which contain short regions for which there are no good triplet matches.
我们通过DNA酶I足迹法研究了四种三链体结合配体对寡脱氧核苷酸T8NT8（N = A、G、C、T）与含有序列A8XA8.T8YT8（X = G、C、T；Y = C、G、A）的DNA片段相互作用的影响。这些配体形成了一系列喹啉衍生物，其在4位带有烷基胺链，在2位带有不同的芳基取代基。这些化合物本身在浓度高达100微摩尔时不会改变DNA双链体的DNA酶I消化作用。在10微摩尔的浓度下，它们增强三链体的形成，将产生清晰足迹所需的寡核苷酸浓度降低多达100倍。除了稳定由特征明确的DNA三联体组成的三链体之外，它们还促进包含中心三联体错配的复合物的形成。三链螺旋形成严格性的这种降低可用于拓宽三链体靶序列的范围，并能够在包含没有良好三联体匹配的短区域的位点进行识别。
