An anion-selective analogue of the channel-forming peptide alamethicin

The peptide alamethicin self-assembles to form helix bundle ion channels in membranes. Previous macroscopic measurements have shown that these channel s are mildly cation-selective. Models indicate that a source of cation sele ctivity is a zone of partial negative charge toward the C-terminal end of t he peptide. We synthesized an alamethicin derivative with a lysine in this zone (replacing the glutamine at position 18 in the sequence). Microscopic (single-channel) measurements demonstrate that dimeric alamethicin-lysine18 (alm-K18) forms mildly anion-selective channels under conditions where cha nnels formed by the parent peptide are cation-selective. Long-range electro static interactions can explain the inversion of ion selectivity and the co nductance properties of alamethicin channels.