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.

中文翻译：

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通过单蛋白纳米孔传感界面探索 G-四链体和卟啉衍生物的相互作用

人类端粒和原癌基因 c-MYC 都可以形成具有各种构象的 G-四链体 (G4)。卟啉衍生物（TMPyP4）可以稳定G4，因此被认为是一种潜在的抗癌药物。在本文中，使用单一蛋白质纳米孔传感界面研究了三种典型的 G4s（端粒篮、端粒杂交 1 和 c-MYC Pu22 平行）的易位行为及其与 TMPyP4 的相互作用，其主要电解质为 0.5 M 四甲基氯化铵. 从电流脉冲的驻留时间统计可以看出，在K+存在下，平行G4比Hybrid-1 G4更稳定，而在Na+存在下，篮子G4的持续时间最短。由于与 TMPyP4 相互作用，所有 G4 的停留时间增加，表明有明显的稳定作用。该研究表明，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，而且还提供了配体的相互作用信息，可用于药物设计。