Development of new DNA nano-switches based on the stabilization of A-T base pairs relative to G-C base pairs

我们尝试使用磷酸胆碱二氢钠的水合离子液体(IL)来控制Watson-Crick碱基对的稳定性，因为水合离子液体是适合于广泛化学反应的绿色溶剂，可以确保生物分子的长期稳定性。我们的定量分析表明，在4M胆碱DHP中，A-T碱基对比G-C碱基对更稳定。我们还发现，与氯化钠溶液相比，在胆碱DHP溶液中，通过形成Hoogsteen碱基对而形成的DNA三链结构显著稳定。热力学分析和分子动力学计算表明，A-T碱基对和Hoogsteen碱基对的稳定是胆碱离子与DNA沟槽特异结合的结果。为了利用三链构型的稳定性来开发双链DNA传感系统，我们设计了一个DNA分子信标，发现该分子信标可以特异性地检测到目标双链。

We attempted the control of stabilities of Watson-Crick base pairs using a hydrated ionic liquid (IL) of choline dihydrogen phosphate (choline dhp), because hydrated ILs are green solvents suitable for a wide range of chemical reactions and may ensure long-term stability of biomolecules. Our quantitative analysis demonstrated that A-T base pairs are more stable than G-C base pairs in 4 M choline dhp. We also found that DNA triplex structures via the formation of Hoogsteen base pairs were significantly stabilized in the choline dhp solution compared to NaCl solutions. Thermodynamic analyses and molecular dynamics calculations revealed that the stabilization of A-T base pairs and Hoogsteen base pairs was due to specific binding of choline ions to DNA grooves. To take advantage of the stabilization of triplex formations to develop the sensing systems of double-stranded DNAs, we designed a DNA molecular beacon and found that the molecular beacon can specifically detect the target duplex.