γ-(S)-Trifluoromethyl proline: evaluation as a structural substitute of proline for solid state 19F-NMR peptide studiesElectronic supplementary information (ESI) available. CCDC 1042476. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5ob00034c

γ-(4 S )-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. γ-( S )-Trifluoromethyl proline has been evaluated as a structural label for solid state 19 F-NMR studies of polypeptides.