NMR Structure and Dynamic Studies of an Anion-Binding, Channel-Forming Heptapeptide

J. Am. Chem. Soc., 128 (5), 1633 -1638, 2006. 10.1021/ja055887j S0002-7863(05)05887-7
Web Release Date: January 12, 2006

NMR Structure and Dynamic Studies of an Anion-Binding, Channel-Forming Heptapeptide

Gabriel A. Cook, Robert Pajewski, Mahalaxmi Aburi, Paul E. Smith, Om Prakash, John M. Tomich, and George W. Gokel*

Contribution from the Departments of Biochemistry and Chemistry, Kansas State University, Manhattan, Kansas 66506, Department of Chemistry, Washington University, 1 Brookings Drive, St. Louis, Missouri 63130, and Department of Molecular Biology & Pharmacology, Washington University School of Medicine, Campus Box 8103, 660 S. Euclid Avenue, St. Louis, Missouri 63110

ggokel@wustl.edu

Received September 6, 2005

Abstract:

The synthetic peptide (C₁₈H₃₇)₂NCOCH₂OCH₂CON-(Gly)₃-Pro-(Gly)₃-OCH₂Ph forms chloride-selective channels in liposomes and exhibits voltage-gating properties in planar phospholipid bilayers. The peptide fragment of the channel is based on a conserved motif in naturally occurring chloride transporters. Membrane-anchoring residues at the N- and C-terminal ends augment the peptide. NMR spectra (1D and 2D) of the channel in CDCl₃ showed significant variation in the absence and presence of stoichiometric tetrabutylammonium chloride (Bu₄NCl). One-dimensional solution-state NMR titration studies combined with computational molecular simulation studies indicate that the peptide interacts with the salt as an ion pair and H-bonds chloride. To our knowledge, this is the first structural analysis of any synthetic anion-channel salt complex.

Download the full text: PDF | HTML