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

Abstract

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.