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 β2/β3- nonapeptide with polar, positively charged side chains was subjected to NMR analysis in MeOH and H2O. Whereas, in MeOH, it folds into a 10/12-helix very similar to the structure determined for a corresponding β2/β3-nonapeptide with only aliphatic side chains, no dominant conformation could be determined in H2O. Finally, the NMR analysis of a β3-icosapeptide containing the side chains of all 20 proteinogenic amino acids in MeOH is described. It revealed that this 20mer folds into a 314-helix over its whole length forming six full turns, the longest 314-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.
ASJC Scopus subject areas
- Drug Discovery
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry