Position effect of cross-strand side-chain interactions on beta-hairpin formation

Previous conformational analysis of 10-residue linear peptides enabled us t o identify some cross-strand side-chain interactions that stabilize beta -h airpin conformations. The stabilizing influence of these interactions appea red to be greatly reduced when the interaction was located at the N- and C- termini of these 10-residue peptides. To investigate the effect of the posi tion relative to the turn of favorable interactions on beta -hairpin format ion, we have designed two 15-residue beta -hairpin forming peptides with th e same residue composition and differing only in the location of two residu es within the strand region. The conformational properties of these two pep tides in aqueous solution were studied by H-1 and C-13 NMR. Differences in the conformational behavior of the two designed 15-residue peptides suggest that the influence of stabilizing factors for beta -hairpin formation, in particular, cross-strand side-chain interactions, depends on their proximit y to the turn. Residues adjacent to the turn are most efficient in that con cern. This result agrees with the proposal that the turn region acts as the driving force in beta -hairpin folding.