Trp-Trp pairs as β-hairpin stabilisers: hydrogen-bonded versus non-hydrogen-bonded sites

Trp-Trp pairs have emerged as a successful strategy for β-hairpin stabilization. Using loop 3 of Vammin as a template, we experimentally demonstrate that the contribution of Trp-Trp pairs to β-hairpin stability depends on β-sheet periodicity, that is, they are stabilising at non-hydrogen-bonded sites, but not at hydrogen-bonded positions.