Mixed β ²/β ³-hexapeptides and β ²/β ³-nonapeptides folding to (P)-helices with alternating twelve- and ten-membered hydrogen-bonded rings

The structural properties of four mixed β-peptides with alternating β ²/β ³- or β ³/β ²-sequences have been analyzed by two-dimensional homonuclear ¹H-NMR- and CD spectroscopic measurements. All four β-peptides fold into (P)-helices with twelve- and ten-membered H-bonded rings (Figs. 3-6). CD Spectra (Fig. 2) of the mixed β ³/β ²-hexapeptide 4a and β ³/β ² -nonapeptide 5a, indicating that peptides of this type also adopt the 12/10-helical conformation, were confirmed by NMR structural analysis. For the deprotected β ³/β ²-nonapeptide 5d, NOEs not consistent with the 10/12 helix have been observed, showing that the stability of the helix decreases upon N-terminal deprotection. From the NMR structures obtained, an idealized helical-wheel representation was generated (Fig. 7), which will be used for the design of further 12/10 or 10/12 helices.