Impact of Strand Length on the Stability of Parallel‐β‐Sheet Secondary Structure

The thousands of tertiary structural motifs known among natural proteins are built up from a handful of regular secondary structures, mostly α helices and β sheets, which are linked by β turns and larger loops. Sequence–stability relationships for α helices[1–3] and for antiparallel β sheets[4–7] have been widely explored using autonomously folding peptides, an experimental approach that eliminates the potentially confounding influence of a specific tertiary context. In contrast, a minimal parallel β sheet cannot readily be generated within a conventional peptide because the N terminus of one strand is necessarily distant from the C terminus of a neighboring strand. A continuous peptide design for a parallel β sheet would require a long interstrand loop, introducing significant tertiary packing effects or an entropic penalty for folding, either of which would compromise the analysis. Thus, novel strategies are required to elucidate the factors that govern parallel-β-sheet stability.[8,9]