Side chain effect on ion channel characters of Aib rich peptides

As models of ion channel proteins and naturally occurring pore-forming pept ides, we designed a series of Aib rich peptides [Ac-(Aib-XXx-Aib-Ala)(5)-NH 2 (Xxx = Lys, Glu, Ser, and Gly: BXBA-20)] to investigate the effects of th e side chains of the amino acid residues Lys, Glu, Ser, and Gly on the conf ormation and electrophysiological properties of ion channels. The conformat ion of peptides and their affinity for phospholipid membranes were evaluate d by CD spectroscopy. Patch-clamp experiments revealed that all BXBA-20 pep tides form ion channels in DPhPC bilayers exhibiting clearly resolved trans itions between the open and closed states. The channel forming frequency wa s in the order BKBA-20 > BEBA-20 > BSBA-20 > BGBA-20. In the case of BIKBA- 20 and BEBA-20, the self-assembled conductive oligomers expressed homogeneo us and voltage-independent single channel conductances. In contrast, hetero geneous conductance was observed in BSBA-20 and BGBA-20 ion channels under similar experimental conditions. From these results, we conclude that pepti des with a high degree of helical conformation, high amphipathicity, high a ffinity for lipid membranes, and self-associating characters in vesicles ar e most suitable for inducing ion channels with a high frequency of occurren ce. Moreover, BEBA-20, BSBA-20, and BGBA-20 channels were cation-selective, whereas the BEBA-20 channel was non-selective.