Graduate School of Phamaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita 565-0871, Japan.
Graduate School of Phamaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita 565-0871, Japan.
Bioorg Med Chem Lett. 2014 Jul 15;24(14):3046-9. doi: 10.1016/j.bmcl.2014.05.031. Epub 2014 May 17.
Several triplex-forming oligonucleotides (TFOs) partially modified with 2'-O-(2-aminoethyl)- or 2'-O-(2-guanidinoethyl)-nucleotides were synthesized and their association rate constants (kon) with double-stranded DNA were estimated by UV spectrophotometry. Introduction of cationic modifications in the 5'-region of the TFOs significantly increased the kon values compared to that of natural TFO, while no enhancement in the rate of triplex DNA formation was observed when the modifications were in the middle and at the 3'-region. The kon value of a TFO with three adjacent cationic modifications at the 5'-region was found to be 3.4 times larger than that of a natural one. These results provide useful information for overcoming the inherent sluggishness of triplex DNA formation.
合成了几种部分用 2'-O-(2-氨基乙基)-或 2'-O-(2-胍基乙基)-核苷酸修饰的三聚体形成寡核苷酸（TFO），并通过紫外分光光度法估计了它们与双链 DNA 的缔合速率常数（kon）。与天然 TFO 相比，TFO 的 5'-区域中引入阳离子修饰显著提高了 kon 值，而当修饰位于中间和 3'-区域时，三链 DNA 形成的速率没有提高。在 5'-区域带有三个相邻阳离子修饰的 TFO 的 kon 值被发现比天然 TFO 的大 3.4 倍。这些结果为克服三链 DNA 形成固有的迟缓性提供了有用的信息。
