Research Center for Analytical Sciences, Chemistry Department, College of Sciences, Northeastern University, Shenyang, 110819, China.
Research Center for Analytical Sciences, Chemistry Department, College of Sciences, Northeastern University, Shenyang, 110819, China.
Anal Chim Acta. 2020 Apr 15;1106:126-132. doi: 10.1016/j.aca.2020.01.053. Epub 2020 Jan 25.
Both human telomere and proto-oncogene c-MYC can form G-quadruplex (G4) with various conformations. Porphyrin derivative (TMPyP4) could stabilize G4, and thus is considered as a potential drug for anticancer therapeutics. In this paper, the translocation behaviors of three typical G4s (telomere basket, telomere hybrid-1 and c-MYC Pu22 parallel) and their interaction with TMPyP4 were investigated with a single protein nanopore sensing interface with the same main electrolyte of 0.5 M tetramethylammonium chloride. As observed by the statistics of the dwell time of the current pulses, in the presence of K, the parallel G4 is more stable than the hybrid-1 G4, while the basket G4 in the presence of Na exhibited shortest duration. The dwell time of all of the G4s increased as the result of interaction with TMPyP4, indicating an obvious stabilizing effect. This study demonstrated that the single nanopore sensing interface not only reveal the stability of various G4 conformations at a single-molecule level, but also provide the interaction information of a ligand, which could be useful in the drug design.
人类端粒和原癌基因 c-MYC 都可以形成具有多种构象的 G-四链体（G4）。卟啉衍生物（TMPyP4）可以稳定 G4，因此被认为是一种有潜力的抗癌治疗药物。在本文中，使用相同的主要电解质 0.5 M 四甲基氯化铵，通过单个蛋白质纳米孔传感界面研究了三种典型 G4（端粒篮、端粒杂交-1 和 c-MYC Pu22 平行）的转位行为及其与 TMPyP4 的相互作用。通过电流脉冲停留时间的统计观察到，在存在 K 的情况下，平行 G4 比杂交-1 G4 更稳定，而在存在 Na 的情况下，篮 G4 的持续时间最短。与 TMPyP4 相互作用后，所有 G4 的停留时间都增加，表明存在明显的稳定作用。这项研究表明，单个纳米孔传感界面不仅在单分子水平上揭示了各种 G4 构象的稳定性，还提供了配体的相互作用信息，这在药物设计中可能很有用。
