Ligand-gated synthetic ion channels.
Supramolecular pi-stack architecture is fundamental in DNA chemistry but absent in biological and synthetic ion channels and pores. Here, a novel rigid-rod pi-stack architecture is introduced to create synthetic ion channels with characteristics that are at the forefront of rational design, that is, ligand gating by a conformational change of the functional supramolecule. Namely, the intercalation of electron-rich aromatics is designed to untwist inactive electron-poor helical pi-stacks without internal space into open barrel-stave ion channels. Conductance experiments in planar lipid bilayers corroborate results from spherical bilayers and molecular modeling: Highly cooperative and highly selective ligand gating produces small, long-lived, weakly anion selective, ohmic ion channels. Structural studies conducted under conditions relevant for function provide experimental support for helix-barrel transition as origin of ligand gating. Control experiments demonstrate that minor structural changes leading to internal decrowding suffice to cleanly annihilate chiral self-organization and function.
Talukdar
Pinaki
P
Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.
Bollot
Guillaume
G
Mareda
Jiri
J
Sakai
Naomi
N
Matile
Stefan
S
D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D008051:Lipid Bilayers; D008958:Models, Molecular; D015394:Molecular Structure
D007473:Ion Channels; D008024:Ligands; D008051:Lipid Bilayers; D004247:DNA