Conformational switching in designed peptides: The helix/sheet transition

Background: The structure adopted by peptides and proteins depends not only on the primary sequence, but also on conditions such as solvent polarity or method of sample preparation. We examined the effect that solution conditions have on the folded conformations of two peptides, one of which contains the photoisomerizable amino acid p-phenylazo-L-phenylalanine. Results: Spectroscopic studies indicate that these two peptides switch between helical and beta sheet conformations. The switch behavior is influenced by solution conditions including pH, NaCl concentration, temperature, and peptide concentration. The CD spectrum of the peptide containing p-phenylazo-L-phenylalanine changes from a spectrum characteristic of a beta sheet to one characteristic of an alpha helix upon irradiation. Conclusions: We hypothesize that the structural states of the peptides are a monomeric alpha helix and an aggregated antiparallel beta sheet; conditions encouraging aggregation tend to favor sheet; conditions discouraging aggregation tend to favor helix. Consideration of such solution-dependent conformational changes may affect de novo protein design and have a bearing on certain biological processes.