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 (~0.4nm). 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 ~50μM) and human neuroblastoma SH-SY5Y cells (IC50 ~60μM), while they were not toxic to gram-negative Escherichia coli bacteria at a concentration up to 500μM. Based on these properties, this drug-like, synthetic, pore-forming molecule with a molecular weight below 500gmol−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. [Copyright &y& Elsevier]