The turn sequence directs β‐ strand alignment in designed β‐hairpins

A previous NMR investigation of model decapeptides with identical β‐strand sequences and different turn sequences demonstrated that, in these peptide systems, the turn residues played a more predominant role in defining the type of β‐hairpin adopted than cross‐strand side‐chain interactions. This result needed to be tested in longer β‐hairpin forming peptides, containing more potentially stabilizing cross‐strand hydrogen bonds and side‐chain interactions that might counterbalance the influence of the turn sequence. In that direction, we report here on the design and ¹H NMR conformational study of three β‐hairpin forming pentadecapeptides. The design consists of adding two and three residues at the N‐ and C‐termini, respectively, of the previously studied decapeptides. One of the designed pentadecapeptides includes a potentially stabilizing R‐E salt bridge to investigate the influence of this interaction on β‐hairpin stability. We suggest that this peptide self‐associates by forming intermolecular salt bridges. The other two pentadecapeptides behave as monomers. A conformational analysis of their ¹H NMR spectra reveals that they adopt different types of β‐hairpin structure despite having identical strand sequences. Hence, the β‐turn sequence drives β‐hairpin formation in the investigated pentadecapeptides that adopt β‐hairpins that are longer than the average protein β‐hairpins. These results reinforce our previous suggestion concerning the key role played by the turn sequence in directing the kind of β‐hairpin formed by designed peptides.