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

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 Pb²⁺ 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 Pb²⁺-stabilized antiparallel isomers, and K⁺-stabilized parallel isomers exhibited significant differences in the transmembrane transport. The former showed high Pb²⁺ transport activity (EC₅₀ = 1.55 μM) and selectivity (Pb²⁺/K⁺ selectivity = 30.6), while the latter demonstrated high K⁺ transport activity (EC₅₀ = 0.56 μM) and selectivity (K⁺/Pb²⁺ 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.