title: Temperature coefficients of amide proton NMR resonance frequencies in trifluoroethanol: a monitor of intramolecular hydrogen bonds in helical peptides.
abstract: 2D 1H NMR spectroscopy of two alpha-helical peptides which differ in their amphipathicity has been used to investigate the relationships between amide-proton chemical shifts, amide-proton exchange rates, temperature, and trifluoroethanol (TFE) concentration. In 50% TFE, in which the peptides are maximally helical, the amide-proton chemical shift and temperature coefficient patterns are very similar to each other in each peptide. Temperature coefficients from -10 to -6 ppb/K, usually indicative of the lack of intramolecular hydrogen bonds, were observed even for hydrophobic amino acids in the center of the alpha-helices. However, slow hydrogen isotope exchange for residues from 4 to 16 in both 18-mer helices indicates intact intramolecular hydrogen bonds over most of the length of these peptides. Based on these anomalous observations, we suggest that the pattern of amide-proton shifts in alpha-helices in H20/TFE solvents is dominated by bifurcated intermolecular hydrogen-bond formation between the backbone carbonyl groups and TFE. The amide-proton chemical shift changes with increasing temperature may be interpreted by a disruption of intermolecular hydrogen bonds between carbonyl groups and the TFE in TFE/water rather than by the length of intramolecular hydrogen bonds in alpha-helices.
authors.affiliation: Research Institute of Molecular Pharmacology, Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Rothemund
authors.forename: H
authors.initials: H
authors.lastname: Weisshoff
authors.forename: M
authors.initials: M
authors.lastname: Beyermann
authors.forename: E
authors.initials: E
authors.lastname: Krause
authors.forename: M
authors.initials: M
authors.lastname: Bienert
authors.forename: C
authors.initials: C
authors.lastname: Mügge
authors.forename: B D
authors.initials: BD
authors.lastname: Sykes
authors.forename: F D
authors.initials: FD
authors.lastname: Sönnichsen
mesh_terms: D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D013696:Temperature; D014270:Trifluoroethanol / Q000737:chemistry*
chemical_list: D010455:Peptides; D014270:Trifluoroethanol; D006859:Hydrogen