Taniguchi Yosuke, Miyazaki Mei, Matsueda Nozomu, Wang Lei, Okamura Hidenori, Sasaki Shigeki
Graduate School of Pharmaceutical Sciences, Kyushu University.
Chem Pharm Bull (Tokyo). 2018;66(6):624-631. doi: 10.1248/cpb.c18-00043.
The antiparallel triplex DNA is formed by the interaction between purine-rich triplex forming oligonucleotides (TFOs) and the homo-purine region within a duplex DNA. The formation of such a structure with the genome DNA promises to control the gene expression in a living cell. In this study, in an attempt to enhance the stability of the triplex DNAs, we have designed the N-arylated deoxyguanosine derivatives. Among these analogues, we found that the TFOs containing N-phenyl-2'-deoxyguanosine (PhdG) showed a stable and selective triplex DNA formation with the GC base pair as compared to the natural dG/GC triplet. However, the multiple incorporation of PhdG into the TFOs hampered the stable triplex DNA, instead, showed a tendency to form a higher order structure. Therefore, we concluded that the stable and selective triplex DNA formation is expected by the replacement of dG by PhdG in the purine-rich TFO sequence.
反平行三链体DNA是由富含嘌呤的三链体形成寡核苷酸（TFO）与双链DNA中的同型嘌呤区域相互作用形成的。这种与基因组DNA形成的结构有望在活细胞中控制基因表达。在本研究中，为了提高三链体DNA的稳定性，我们设计了N-芳基化脱氧鸟苷衍生物。在这些类似物中，我们发现与天然dG/GC三联体相比，含有N-苯基-2'-脱氧鸟苷（PhdG）的TFO与GC碱基对形成了稳定且选择性的三链体DNA。然而，将PhdG多次掺入TFO中阻碍了稳定的三链体DNA形成，反而显示出形成更高阶结构的趋势。因此，我们得出结论，通过在富含嘌呤的TFO序列中用PhdG取代dG有望形成稳定且选择性的三链体DNA。
