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.