Self-assembled, cation-selective ion channels from an oligo(ethylene glycol) derivative of benzothiazole aniline

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 (EG(4)) moiety. Macroscopic and single-channel current recordings suggest that these pores are formed by the assembly of four BTA-EG(4) monomers with an open pore diameter that appears similar to the one of gramicidin pores (similar to 0.4 nm). The single-channel conductance of these pores is modulated by the pH of the electrolyte and has a minimum at pH similar to 3. Self-assembled pores from BTA-EG(4) are selective for monovalent cations and have long open channel lifetimes on the order of seconds. BTA-EG(4) 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-EG(4) molecules inhibited growth of gram-positive Bacillus subtilis bacteria (IC50 similar to 50 mu M) and human neurobiastoma SH-SY5Y cells (IC50 similar to 60 mu M), while they were not toxic to gram-negative Escherichia colt bacteria at a concentration up to 500 mu M. 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-EG(4) molecules offer an example of a self-assembled synthetic supramolecule with biological function. (C) 2011 Elsevier B.V. All rights reserved.