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-p henylalanine. Results: Spectroscopic studies indicate that these two p eptides switch between helical and beta sheet conformations. The switc h behavior is influenced by solution conditions including pH, NaCl con centration, temperature, and peptide concentration. The CD spectrum of the peptide containing p-phenylazo-L-phenylalanine changes from a spe ctrum characteristic of a beta sheet to one characteristic of an alpha helix upon irradiation. Conclusions: We hypothesize that the structur al states of the peptides are a monomeric alpha helix and an aggregate d 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 af fect de novo protein design and have a bearing on certain biological p rocesses.