title: Engineering stabilized ion channels: covalent dimers of alamethicin.
abstract: The peptide alamethicin forms channels with a variety of conductance states. Selective stabilization of a particular state should simplify the task of understanding conductance in terms of channel structure. We synthesized two different covalent dimers of alamethicin in which peptides were linked at their C-terminal ends by flexible tethers. Both dimeric peptides formed channels with conductances that matched those of alamethicin channels. Particular conductance states were selectively stabilized, however, with lifetimes up to 170-fold longer than the same states observed with monomers. In addition, tethering appeared to limit the size of the structures formed so that, even at higher peptide concentrations, a single predominant conductance state was obtained. We suggest this state corresponds to a channel made from six alamethicin molecules (three dimers).
authors.affiliation: Department of Chemistry, University of Toronto, Canada.
authors.forename: S
authors.initials: S
authors.lastname: You
authors.forename: S
authors.initials: S
authors.lastname: Peng
authors.forename: L
authors.initials: L
authors.lastname: Lien
authors.forename: J
authors.initials: J
authors.lastname: Breed
authors.forename: M S
authors.initials: MS
authors.lastname: Sansom
authors.forename: G A
authors.initials: GA
authors.lastname: Woolley
mesh_terms: D000408:Alamethicin / Q000138:chemical synthesis / Q000737:chemistry*; D000595:Amino Acid Sequence; D004355:Drug Stability; D004553:Electric Conductivity; D066298:In Vitro Techniques; D007473:Ion Channels / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D015202:Protein Engineering
chemical_list: D007473:Ion Channels; D000408:Alamethicin