Abstract
The NMR‐solution structure of an α‐heptapeptide with a central Aib residue was investigated in order to verify that, in contrast to β‐peptides, short α‐peptides do not form a helical structures in MeOH. Although the central Aib residue was found to induce a bend in the experimentally determined structure, no secondary structure typical for longer α‐peptides or proteins was found. A β^2^/β^3^‐nonapeptide with polar, positively charged side chains was subjected to NMR analysis in MeOH and H~2~O. Whereas, in MeOH, it folds into a 10/12‐helix very similar to the structure determined for a corresponding β^2^/β^3^‐nonapeptide with only aliphatic side chains, no dominant conformation could be determined in H~2~O. Finally, the NMR analysis of a β^3^‐icosapeptide containing the side chains of all 20 proteinogenic amino acids in MeOH is described. It revealed that this 20mer folds into a 3~14~‐helix over its whole length forming six full turns, the longest 3~14~‐helix found so far. Together, our findings confirm that, in contrast to α‐peptides, β‐peptides not only form helices with just six residues, but also form helices that are longer than helical sections usually observed in proteins or natural peptides. The higher helix‐forming propensity of long β‐peptides is attributed to the conformation‐stabilizing effect of the staggered ethane sections in β‐peptides which outweighs the detrimental effect of the increasing macrodipole.