Recognition of polarized lipid bilayers by p-oligophenyl ion channels: from push-pull rods to push-pull barrels.

Design, synthesis, and evaluation of 14-methoxy-84-methylsulfonyl-22,33,42,53,62,73-hexa(Gla-Leu-Lys-Leu-NH2)-p-octiphenyl (1) and 14,84-bismethoxy-22,33,42,53,62,73-hexa(Gla-Leu-Lys-Leu-NH2)-p-octiphenyl (2) are described (Gla = -OCH2CO-). Nanomolar concentrations of push-pull rod 1 are found to suffice to selectively form ion channels in polarized spherical bilayer membranes composed of egg yolk phosphatidylcholine. Exponential dependence of the ion-channel activity on membrane polarization reveals a gating charge of 0.85/channel. Independence of the activity of push-push rod 2 on membrane potential demonstrates that cell membrane recognition originates from the axial dipole in push-pull rod 1. Nonlinear concentration dependence of activity at -180 mV indicates parallel self-assembly of push-pull rod 1 into a tetrameric barrel-stave supramolecule.