title: Self-assembled, cation-selective ion channels from an oligo(ethylene glycol) derivative of benzothiazole aniline.
abstract: This paper describes the spontaneous formation of well-defined pores in planar lipid bilayers from the self-assembly of a small synthetic molecule that contains a benzothiazole aniline (BTA) group attached to a tetra-ethylene glycol (EG4) moiety. Macroscopic and single-channel current recordings suggest that these pores are formed by the assembly of four BTA-EG4 monomers with an open pore diameter that appears similar to the one of gramicidin pores (~0.4 nm). The single-channel conductance of these pores is modulated by the pH of the electrolyte and has a minimum at pH~3. Self-assembled pores from BTA-EG4 are selective for monovalent cations and have long open channel lifetimes on the order of seconds. BTA-EG4 monomers in these pores appear to be arranged symmetrically across both leaflets of the bilayer, and spectroscopy studies suggest that the fluorescent BTA group is localized inside the lipid bilayers. In terms of biological activity, BTA-EG4 molecules inhibited growth of gram-positive Bacillus subtilis bacteria (IC50~50 μM) and human neuroblastoma SH-SY5Y cells (IC50~60 μM), while they were not toxic to gram-negative Escherichia coli bacteria at a concentration up to 500 μM. Based on these properties, this drug-like, synthetic, pore-forming molecule with a molecular weight below 500 g mol(-1) might be appealing as a starting material for development of antibiotics or membrane-permeating moieties for drug delivery. From a biophysical point of view, long-lived, well-defined ion-selective pores from BTA-EG4 molecules offer an example of a self-assembled synthetic supramolecule with biological function.
authors: Department of Biomedical Engineering, University of Michigan, 1101 Beal Avenue, Ann Arbor, Michigan 48109-2110, USA.
authors: Panchika
authors: P
authors: Prangkio
authors: Divya K
authors: DK
authors: Rao
authors: Kevin D
authors: KD
authors: Lance
authors: Mark
authors: M
authors: Rubinshtein
authors: Jerry
authors: J
authors: Yang
authors: Michael
authors: M
authors: Mayer
mesh_terms: D052160:Benzothiazoles / Q000737:chemistry*; D002412:Cations; D045744:Cell Line, Tumor; D005026:Ethylene Glycols / Q000737:chemistry*; D006801:Humans; D007473:Ion Channels / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D052160:Benzothiazoles; D002412:Cations; D005026:Ethylene Glycols; D007473:Ion Channels