Conformational and orientation studies of artificial ion channels incorporated into lipid bilayers

The conformational and orientation studies in lipid bilayers of 21 amino ac id peptides bearing six crown ethers are reported. The compounds were desig ned to form artificial ion channels by stacking the crown rings, and were s hown to be functional in bilayer membranes. We used Fourier transform infra red spectroscopy and CD spectropolarimetry to study the conformation of the peptides in solution and in lipid bilayers. These studies revealed that he xacrown peptides retain their alpha -helical conformation when incorporated in a lipid bilayer environment. Attenuated total reflectance spectroscopy was used to investigate the orientation of the peptides in a lipid bilayer. Results demonstrated that the peptides are not oriented at a fixed angle i n membrane, but rather are in incorporation equilibrium between an active s tate parallel to the lipid chain and an inactive state adsorbed at the surf ace of the bilayer. From these results, we propose a model for the channel activity and the gating mechanism of these hexacrown peptides in bilayer me mbranes. (C) 2001 John Wiley & Sons, Inc.