Kukreti S, Sun J S, Loakes D, Brown D M, Nguyen C H, Bisagni E, Garestier T, Helene C
Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, INSERM U201, CNRS URA481, 43 rue Cuvier, 75231 Paris Cedex 05, France.
Nucleic Acids Res. 1998 May 1;26(9):2179-83. doi: 10.1093/nar/26.9.2179.
Oligonucleotide-directed triple helix formation is mostly restricted to oligopyrimidineoligopurine sequences of double helical DNA. An interruption of one or two pyrimidines in the oligopurine target strand leads to a strong triplex destabilisation. We have investigated the effect of nucleotide analogues introduced in the third strand at the site opposite the base pair inversion(s). We show that a 3-nitropyrrole derivative (M) discriminates GC from CG, AT and TA in the presence of a triplex-specific ligand (a benzo[e]pyridoindole derivative, BePI). N6-methoxy-2,6-diaminopurine (K) binds to an AT base pair better than a TA, GC or C*G base pair. Some discrimination is still observed in the presence of BePI and triplex stability is markedly increased. These findings should help in designing BePI-oligonucleotide conjugates to extend the range of DNA sequences available for triplex formation.
寡核苷酸定向三链螺旋的形成大多局限于双链DNA的寡嘧啶寡嘌呤序列。寡嘌呤靶链中一个或两个嘧啶的中断会导致三链体强烈失稳。我们研究了在与碱基对倒置位点相对的位置引入到第三条链中的核苷酸类似物的作用。我们发现，在存在三链体特异性配体（一种苯并[e]吡啶吲哚衍生物，BePI）的情况下，一种3-硝基吡咯衍生物（M）能够区分GC与CG、AT和TA。N6-甲氧基-2,6-二氨基嘌呤（K）与AT碱基对比与TA、GC或C*G碱基对结合得更好。在存在BePI的情况下仍能观察到一些区分，并且三链体稳定性显著增加。这些发现应有助于设计BePI-寡核苷酸缀合物，以扩大可用于形成三链体的DNA序列范围。
