Lipophilic G-Quadruplex Isomers as Biomimetic Ion Channels for Conformation-Dependent Selective Transmembrane Transport.

Transport selectivity is a challenge in the design of biomimetic transmembrane channels. In the present study, specific ion-dependent lipophilic G-quadruplexes displaying different conformations were designed for the construction of highly selective artificial transmembrane channels. The presence of Pb and K ions prompted the folding of lipophilic PS2.M sequence into G-quadruplexes with antiparallel and parallel conformations. Membrane immobilization of the G-quadruplex channels restricted the reversible configurational changes between different topologies, which was confirmed by Förster resonance energy transfer (FRET) analysis. 8-Hydroxypyrene-1,3,6-trisulfonic acid (HPTS) transport assays revealed that Pb-stabilized antiparallel isomers, and K-stabilized parallel isomers exhibited significant differences in the transmembrane transport. The former showed high Pb transport activity (EC = 1.55 μM) and selectivity (Pb/K selectivity = 30.6), while the latter demonstrated high K transport activity (EC = 0.56 μM) and selectivity (K/Pb selectivity = 31.8). The cation selectivity of these channel mimics was also consistent with the outcomes of the conducted fluorescent probe assays. The results described herein provide a platform for effective development of conformation-dependent ion-selective biomimetic transmembrane channels. The G-quadruplex channels demonstrate high potential for application in the fields of molecular diagnostics, logic biocomputing, selective separation, and single-molecule biosensing.