Structural Rearrangement from Oligomer to Fibril Detected with FRET in a Designed Amphiphilic Peptide.

β-Sheet conformation is promoted in peptides with amphiphilic design, and stable β-turn formation is favored with the unnatural amino acid d-Pro followed by a flexible residue such as Gly. A 19-residue peptide (B3) was synthesized with alternating hydrophobic and hydrophilic residues connected by symmetrical d-Pro-Gly and Gly-d-Pro turns. B3 forms an oligomeric aggregate, rich in β-sheet conformation, that reversibly transforms into an unordered structure on heating, as evidenced by its temperature-dependent IR spectra. When a dansyl moiety was added to the N terminus of B3, the resulting peptide (B3D) can convert into a fibrillar structure after higher temperature incubation, as detected spectroscopically as well as by TEM. The fibrillization process involves an initial unfolding step monitored by the quenching of dansyl emission; in contrast, subsequent enhanced thioflavin T emission is seen on its binding to the fibril. A possible mechanism is proposed: B3D forms a low-temperature oligomer, which is at least partially unfolded by heat and subsequently reassembles more slowly as a fibril.