title: Template-free self-assembling fullerene and lipopeptide conjugates of alamethicin form voltage-dependent ion channels of remarkable stability and activity.
abstract: N- and C-terminally modified with fullerene or lipopeptide alamethicin molecules were designed for the formation of template-free, self-assembling, voltage-dependent ion conducting channels. The automated solid phase synthesis of the alamethicin-F30 sequence was performed by in situ fluoride activation on 2-chlorotritylchloride-polystyrene resin and the conjugation with fullerenes-C60 and -C70 was carried out in solution. Voltage-dependent bilayer experiments revealed preferred channel sizes for C-terminal alamethicin F30-fullerene-C60 and -C70 conjugates and higher activity compared with native alamethicin, whereas N-terminally linked fullerene balls destabilize pore formation. C-terminal alamethicin F30-fullerene-C70 conjugates show pore states with remarkably long lifetimes of seconds. C-terminal lipopeptide conjugates of alamethicin were prepared by coupling via short peptide spacers with synthetic tripalmitoyl-S-glyceryl-cysteine. which represents the strong membrane anchoring N-terminus of bacterial lipoprotein. Alamethicin-lipopeptide conjugates exhibit high channel forming activities, whereby they self-assemble and adopt preferred pore states with extremely long lifetimes. The novel membrane modifying peptaibol constructs are valuable lead compounds for developments in sensorics related to transmembrane ion conductance.
authors.affiliation: Institute of Organic Chemistry, University of Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany. guenther.jung@uni-tuebingen.de
authors.forename: Günther
authors.initials: G
authors.lastname: Jung
authors.forename: Thomas
authors.initials: T
authors.lastname: Redemann
authors.forename: Karsten
authors.initials: K
authors.lastname: Kroll
authors.forename: Sabine
authors.initials: S
authors.lastname: Meder
authors.forename: Andreas
authors.initials: A
authors.lastname: Hirsch
authors.forename: Günther
authors.initials: G
authors.lastname: Boheim
mesh_terms: D000408:Alamethicin / Q000737:chemistry*; D003432:Cross-Linking Reagents; D004355:Drug Stability; D004594:Electrophysiology; D037741:Fullerenes / Q000737:chemistry*; D007473:Ion Channels / Q000138:chemical synthesis*; D008051:Lipid Bilayers; D008074:Lipoproteins / Q000737:chemistry*; D018716:Molecular Mimicry
chemical_list: D003432:Cross-Linking Reagents; D037741:Fullerenes; D007473:Ion Channels; D008051:Lipid Bilayers; D008074:Lipoproteins; C069836:fullerene C70; D000408:Alamethicin; C069837:fullerene C60