title: γ-(S)-Trifluoromethyl proline: evaluation as a structural substitute of proline for solid state (19)F-NMR peptide studies.
abstract: γ-(4S)-Trifluoromethyl proline was synthesised according to a modified literature protocol with improved yield on a multigram scale. Conformational properties of the amide bond formed by the amino acid were characterised using N-acetyl methyl ester model. The amide populations (s-trans vs. s-cis) and thermodynamic parameters of the isomerization were found to be similar to the corresponding values for intact proline. Therefore, the γ-trifluoromethyl proline was suggested as a structurally low-disturbing proline substitution in peptides for their structural studies by (19)F-NMR. Indeed, the exchange of native proline for γ-trifluoromethyl proline in the peptide antibiotic gramicidin S was shown to preserve the overall amphipathic peptide structure. The utility of the amino acid as a selective (19)F-NMR label was demonstrated by observing the re-alignment of the labelled gramicidin S in oriented lipid bilayers.
authors.affiliation: Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany. anne.ulrich@kit.edu and Institute of Chemistry, Technical University of Berlin, Müller-Breslau-Str. 10, 10623 Berlin, Germany.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kubyshkin
authors.affiliation: Institute of Biological Interfaces (IBG-2), KIT, POB 3640, 76021 Karlsruhe, Germany.
authors.forename: Sergii
authors.initials: S
authors.lastname: Afonin
authors.affiliation: Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany. anne.ulrich@kit.edu.
authors.forename: Sezgin
authors.initials: S
authors.lastname: Kara
authors.affiliation: Institute of Chemistry, Technical University of Berlin, Müller-Breslau-Str. 10, 10623 Berlin, Germany.
authors.forename: Nediljko
authors.initials: N
authors.lastname: Budisa
authors.affiliation: Faculty of Chemistry, Taras Shevchenko National University of Kyiv, vul. Volodymyrska 62a, 01601 Kyiv, Ukraine. pavel.mykhailiuk@gmail.com pavel.mykhailiuk@mail.enamine.net and Enamine Ltd., vyl. Chervonotkatska 78, 02660 Kyiv, Ukraine.
authors.forename: Pavel K
authors.initials: PK
authors.lastname: Mykhailiuk
authors.affiliation: Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany. anne.ulrich@kit.edu and Institute of Biological Interfaces (IBG-2), KIT, POB 3640, 76021 Karlsruhe, Germany.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D006096:Gramicidin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; C000601330:gamma-(4S)-trifluoromethyl proline; D006096:Gramicidin; D005461:Fluorine; D011392:Proline