School of Chemical Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, West Bengal, India.
Nat Commun. 2020 Jan 24;11(1):469. doi: 10.1038/s41467-019-13834-7.
The selective transport of ions across cell membranes, controlled by membrane proteins, is critical for a living organism. DNA-based systems have emerged as promising artificial ion transporters. However, the development of stable and selective artificial ion transporters remains a formidable task. We herein delineate the construction of an artificial ionophore using a telomeric DNA G-quadruplex (h-TELO) and a lipophilic guanosine (MG). MG stabilizes h-TELO by non-covalent interactions and, along with the lipophilic side chain, promotes the insertion of h-TELO within the hydrophobic lipid membrane. Fluorescence assays, electrophysiology measurements and molecular dynamics simulations reveal that MG/h-TELO preferentially transports K-ions in a stimuli-responsive manner. The preferential K-ion transport is presumably due to conformational changes of the ionophore in response to different ions. Moreover, the ionophore transports K-ions across CHO and K-562 cell membranes. This study may serve as a design principle to generate selective DNA-based artificial transporters for therapeutic applications.
细胞膜上的离子选择性转运是生物体生存的关键，这由膜蛋白控制。基于 DNA 的系统已成为有前途的人工离子转运体。然而，开发稳定且具有选择性的人工离子转运体仍然是一项艰巨的任务。本研究使用端粒 DNA G-四链体（h-TELO）和疏水性鸟苷（MG）构建了一种人工离子载体。MG 通过非共价相互作用稳定 h-TELO，并与疏水性侧链一起促进 h-TELO 插入疏水性脂质膜内。荧光测定、电生理学测量和分子动力学模拟表明，MG/h-TELO 以刺激响应的方式优先运输 K-离子。这种优先运输 K-离子的现象可能归因于离子载体对不同离子的响应而发生的构象变化。此外，该离子载体还能跨 CHO 和 K-562 细胞膜转运 K-离子。该研究可为治疗应用生成选择性 DNA 基人工转运体提供设计原理。
