Thionoglycine as a multifunctional spectroscopic reporter of screw-sense preference in helical foldamers

A single thionoglycine (glycine thioamide, -HNCH2C(S)-) residue inserted into a peptide foldamer provides both a pair of germinal protons for use as a 1H NMR stereochemical probe and a chromophore giving rise to a well defined Cotton effect in CD. Comparison of the response of these two features to a local helically chiral environment validates them as independent methods for quantifying the conformational screw-sense preference of a helical oligomer, in this case a peptide made of repeated Aib units. The sign of the Cotton effect provides a measure of the sign of the screw-sense preference, while both the chemical shift separation of the anisochronous signals of the glycine CH2 group and the magnitude of the Cotton effect give an estimate of the helicity excess of the oligomer. The thionoglycine unit is readily introduced synthetically by a thionation of a BocGlyAibOMe dipeptide. © 2014 The Royal Society of Chemistry.