γ-(S)-Trifluoromethyl proline: evaluation as a structural substitute of proline for solid state 19F-NMR peptide studies

Vladimir Kubyshkin; Sergii Afonin; Sezgin Kara; Nediljko Budisa; Pavel K. Mykhailiuk; Anne S. Ulrich

doi:10.1039/C5OB00034C

γ-(S)-Trifluoromethyl proline: evaluation as a structural substitute of proline for solid state ¹⁹F-NMR peptide studies†

Vladimir Kubyshkin,^ab Sergii Afonin,^c Sezgin Kara,^a Nediljko Budisa,^b Pavel K. Mykhailiuk*^de and Anne S. Ulrich*^ac

Author affiliations

* Corresponding authors

^a Institute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
E-mail: anne.ulrich@kit.edu

^b Institute of Chemistry, Technical University of Berlin, Müller-Breslau-Str. 10, 10623 Berlin, Germany

^c Institute of Biological Interfaces (IBG-2), KIT, POB 3640, 76021 Karlsruhe, Germany

^d Faculty of Chemistry, Taras Shevchenko National University of Kyiv, vul. Volodymyrska 62a, 01601 Kyiv, Ukraine
E-mail: pavel.mykhailiuk@gmail.com, pavel.mykhailiuk@mail.enamine.net

^e Enamine Ltd., vyl. Chervonotkatska 78, 02660 Kyiv, Ukraine

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 ¹⁹F-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 ¹⁹F-NMR label was demonstrated by observing the re-alignment of the labelled gramicidin S in oriented lipid bilayers.

Supplementary files

Article information

DOI: https://doi.org/10.1039/C5OB00034C
Article type: Paper
Submitted: 07 Jan 2015
Accepted: 13 Feb 2015
First published: 13 Feb 2015
This article is Open Access

Download Citation

Org. Biomol. Chem., 2015,13, 3171-3181

Permissions

Request permissions

γ-(S)-Trifluoromethyl proline: evaluation as a structural substitute of proline for solid state ¹⁹F-NMR peptide studies

V. Kubyshkin, S. Afonin, S. Kara, N. Budisa, P. K. Mykhailiuk and A. S. Ulrich, Org. Biomol. Chem., 2015, 13, 3171 DOI: 10.1039/C5OB00034C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Organic & Biomolecular Chemistry

γ-(S)-Trifluoromethyl proline: evaluation as a structural substitute of proline for solid state ¹⁹F-NMR peptide studies†

Abstract

Supplementary files

Article information

Download Citation

Permissions

γ-(S)-Trifluoromethyl proline: evaluation as a structural substitute of proline for solid state ¹⁹F-NMR peptide studies

Social activity

Search articles by author

Spotlight

Advertisements

Organic & Biomolecular Chemistry