The turn sequence directs beta-strand alignment in designed beta-hairpins

A previous NMR investigation of model decapeptides with identical beta-stra nd sequences and different turn sequences demonstrated that, in these pepti de systems, the turn residues played a more predominant role in defining th e type of beta-hairpin adopted than cross-strand side-chain interactions. T his result needed to be tested in longer beta-hairpin forming peptides, con taining more potentially stabilizing cross-strand hydrogen bands and side-c hain interactions that might counterbalance the influence of the turn seque nce, in that direction, we report hen on the design and H-1 NMR conformatio nal study of three beta-hairpin forming pentadecapeptides. The design consi sts of adding two and three residues at the N- and C-termini, respectively, of the previously studied decapeptides. One of the designed pentadecapepti des includes a potentially stabilizing R-E salt bridge to investigate the i nfluence of this interaction on beta-hairpin stability. We suggest that thi s peptide self-associates by forming intermolecular salt bridges. The other two pentadecapeptides behave as monomers. A conformational analysis of the ir H-1 NMR spectra reveals that they adopt different types of beta-hairpin structure despite having identical strand sequences. Hence, the beta-turn s equence drives beta-hairpin formation in the investigated pentadecapeptides that adopt beta-hairpins that are longer than the average protein beta-hai rpins. These results reinforce our previous suggestion concerning the key r ole played by the turn sequence in directing the kind of beta-hairpin forme d by designed peptides.