Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
Org Biomol Chem. 2011 Jul 21;9(14):5272-9. doi: 10.1039/c1ob05469d. Epub 2011 Jun 3.
The bridged nucleic acid (BNA) containing a thiol at the 6'-position in the bridged structure was synthesized from the disulfide-type BNA and conjugated with various functional molecules via the thioether or the disulfide linkage post-synthetically and efficiently in solution phase. The disulfide-linked conjugate was cleaved under reductive conditions derived from glutathione and an oligonucleotide bearing a free thiol was released smoothly. Conjugated functional molecules had great effects on duplex stability with the DNA complement. In contrast, the molecules little influenced the stability with the RNA complement. Moreover, the oligonucleotides with functional groups at the 6'-position had as high or higher resistances against 3'-exonuclease than phosphorothioate oligonucleotide (S-oligo).
桥连核酸（BNA）在桥连结构的 6'位含有巯基，可通过二硫键型 BNA 与各种功能分子进行有效连接，通过硫醚键或二硫键连接，在溶液相中进行高效的合成后修饰。在还原条件下（来源于谷胱甘肽），二硫键连接的共轭物被切割，自由巯基的寡核苷酸可顺利释放。共轭的功能分子对与 DNA 互补的双链稳定性有很大影响。相比之下，这些分子与 RNA 互补的稳定性影响较小。此外，在 6'位具有官能团的寡核苷酸对 3'外切酶的抗性与硫代磷酸酯寡核苷酸（S-oligo）相当或更高。
