Synthetic potential-dependent transmembrane channels

Synthetic membranophilic, α-helical polypeptides were structurally modified and their self-assembly forming experimental ion channels in lipidbilayer membranes was studied. Biophysical investigations of the channel properties (G.Boheim) allowed the proposal  of a molecular model for the potential-dependent current fluctuations. The α-helices were stabilized by incorporation of α-aminoisobutyric acid (Aib) residues as found in the natural channel former alamethicin. Time-resolved fluorescence spectroscopy, many X-ray analyses, 2D-NMR, CD, and molecular dynamics simulations supported the structure-activity studies.  A most interesting enantiotopomerization has been detected by NMR of 310-helical Aib oligomers.

Enantiotopomerisation of 310-helical (Aib)n homopeptides

Alamethicin Fullerene Conjugate

Single channel current fluctuation pattern of synthetic alamethicin F30

H. Schmitt and G. Jung (1985). Total Synthesis of the αHelical Eicosapeptide Antibiotic Alamethicin, Liebigs Ann. Chem. 1985, 321-344.

R. Bosch, H. Schmitt, G. Jung, and W. Winter (1985). Crystal Structure of the αHelical Undecapeptide Boc-L-Ala-Aib-Ala-Aib-Ala-Glu(OBzl)-Ala-Aib-Ala-Aib-Ala-OMe, Biopolymers 24, 961-979.

G. Menestrina, K.-P. Voges, G. Jung, and G. Boheim (1986). Voltage-Dependent Channel Formation by Rods of Helical Polypeptides, J. Membrane Biol. 93,111-132.

K.-P. Voges, G. Jung, and W. H. Sawyer (1987). Depth-Dependent Fluorescence Quenching of a Tryptophan Residue Located at Defined Positions on a Rigid 2I-Peptide Helix in Liposomes, Biochim. Biophys. Acta 896,64-76.

R.P. Hummel, C. Toniolo, and G. Jung (1987). Conformational Transitions Between Enantiomeric 310-Helices, Angew. Chem. 99, 1180-1182; Angew. Chem. Int. Ed. Engl. 26, 1150-1152.

H.Vogel,  L. Nilsson, R. Rigler, K.-P. Voges, and G. Jung (1988). Structural Fluctuations of a Helical Polypeptide Traversing a Lipid Bilayer, Proc. Natl. Acad. Sci. USA 85, 5067-5071.

H. Vogel, L. Nilsson, R. Rigler, S. Meder, G. Boheim, W. Beck, H.-H. Kurth, and G.
Jung (1993). Structural Fluctuations Between Two Conformational States of a Transmembrane Helical Peptide Are Related to its Channel-Forming Properties in Planar Lipid Membranes, Eur. J. Biochem. 212, 305-313.

G. Jung, T. Redemann, S. Meder, A. Hirsch, and G. Boheim (2003). Template-Free Self-Assembling Fullerene and Lipopeptide Conjugates of Alamethicin Form Voltage-Dependent Ion Channels of Remarkable Stability and Activity, J. Peptide Sci. 9, 784-798.

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