Aoki Eriko, Taniguchi Yosuke, Togo Mieko, Sasaki Shigeki
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Nucleic Acids Symp Ser (Oxf). 2006(50):185-6. doi: 10.1093/nass/nrl092.
Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA-binding agents, but their recognizable duplexes are limited to homopurine/homopyrimidine sequences because of interruption of pyrimidine base in the purine strand. This problem has not been fully solved despite numerous studies. We have previously reported that the novel nucleoside analogues (WNA: W-shaped nucleoside analogues), WNA-betaT and WNA-betaC, can recognize a TA and a CG interrupting sites to form triplexes with high stability and selectively, respectively. However, further investigations have shown that the triplex formation using the WNA derivatives is dependent on its neighbouring bases of the TFOs. In this study, the new WNA analogues having a variety aromatic ring were synthesized to evaluate effects on sequence dependency. And it was found that changes in the substituent of aromatic ring of WNA derivatives altered the binding selectivity and stability in the triplex formation.
三链形成寡核苷酸(TFOs)是序列特异性的DNA结合剂,但由于嘌呤链中嘧啶碱基的中断,它们可识别的双链仅限于同型嘌呤/同型嘧啶序列。尽管进行了大量研究,这个问题仍未得到完全解决。我们之前报道过,新型核苷类似物(WNA:W形核苷类似物)WNA-βT和WNA-βC能够分别识别TA和CG中断位点,以高稳定性和选择性形成三链体。然而,进一步研究表明,使用WNA衍生物形成三链体取决于TFOs的相邻碱基。在本研究中,合成了具有多种芳香环的新型WNA类似物,以评估其对序列依赖性的影响。结果发现,WNA衍生物芳香环取代基的变化改变了三链体形成中的结合选择性和稳定性。