Ionophore constructed from non-covalent assembly of a G-quadruplex and liponucleoside transports K+-ion across biological membranes
Manish Debnath, Sandipan Chakraborty, Y. Pavan Kumar, Ritapa Chaudhuri, Biman Jana, Jyotirmayee Dash
Abstract
Abstract 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.