Department of Chemistry, National Taiwan University, Academia Sinica, Taipei 106, Taiwan, ROC.
Nucleic Acids Res. 2012 Sep 1;40(17):8711-20. doi: 10.1093/nar/gks578. Epub 2012 Jun 26.
Because various non-parallel G-quadruplexes of human telomeric sequences in K+ solution can be converted to a parallel G-quadruplex by adding polyethylene glycol (PEG) as a co-solvent, we have taken advantage of this property of PEG to study the covalent attachment of a PEG unit to a G-quadruplex ligand, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC). The hybrid ligand with the PEG unit, BMVC-8C3O or BMVC-6C2O by substituting either the tetraethylene glycol or the triethylene glycol terminated with a methyl-piperidinium cation in N-9 position of BMVC, not only induces structural change from different non-parallel G-quadruplexes to a parallel G-quadruplex but also increases the melting temperature of human telomeres in K+ solution by more than 45°C. In addition, our ligand work provides further confidence that the local water structure plays the key to induce conformational change of human telomere.
由于在 K+溶液中，人类端粒序列的各种非平行 G-四链体可以通过添加聚乙二醇（PEG）作为共溶剂转化为平行 G-四链体，我们利用 PEG 的这种特性来研究 PEG 单元与 G-四链体配体 3,6-双（1-甲基-4-乙烯基吡啶鎓）咔唑二碘化物（BMVC）的共价连接。具有 PEG 单元的杂交配体，BMVC-8C3O 或 BMVC-6C2O 通过取代 BMVC 中 N-9 位的四乙二醇或三乙二醇末端的甲基-哌啶鎓阳离子，不仅诱导结构从不同的非平行 G-四链体转变为平行 G-四链体，而且使 K+溶液中人类端粒的熔点升高超过 45°C。此外，我们的配体工作进一步证实了局部水分子结构在诱导人类端粒构象变化中起着关键作用。
