title: Ligand-gated synthetic ion channels.
abstract: 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.
authors.affiliation: Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.
authors.forename: Pinaki
authors.initials: P
authors.lastname: Talukdar
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bollot
authors.forename: Jiri
authors.initials: J
authors.lastname: Mareda
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakai
authors.forename: Stefan
authors.initials: S
authors.lastname: Matile
mesh_terms: 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
chemical_list: D007473:Ion Channels; D008024:Ligands; D008051:Lipid Bilayers; D004247:DNA