ABSTRACT
Amyloid deposits have been found to be abundant in patients with Alzheimer's disease due to fibril formation by the Aß peptides. Peptide Aß16-22, comprising of the seven-residue segment KLVFFAE, spanning residues 16-22 of the full length Aß42 peptide, aggregates to form fibrils or other nanostructures in isolation, depending on the conditions of dissolution and incubation. In this study, we have examined the self-assembly of PAß, a tandem repeat peptide of the Aß16-22 sequence, joined by a ß-turn-inducing sequence Asn-Gly. To study the effect of various solvents on the self-association, hexafluoroisopropanol (HFIP), trifluoroethanol (TFE) and methanol were used. The peptide was also incubated in fibril-promoting conditions of 20% fluorinated alcohol-water mixtures which form dynamical solvent clusters, as well as in 20% MeOH-water mixture which does not form solvent clusters. Secondary structural studies suggest the presence of ß-structures. Electron microscopic images indicate that fibril formation occurs in a time-dependent manner, under different conditions of solvent composition. Thioflavin-T fluorescence studies confirm the presence of amyloid fibrils in the aggregates. Although the insertion of the Asn-Gly sequence has not facilitated the formation of an ideal Type I' rigid turn, the intramolecular interactions aid the formation of a flexible ß-turn conformation, with twisted ß-sheets. Interactions between the intermolecular ß-sheets result in the formation of amyloid fibrils. Organic solvents appear to play an important role in modulating self-assembly of peptide PAß during fibril formation. Studies on ß-hairpin engineered amyloidogenic peptides could lead to knowledge about suitable conditions for generating a diverse range of polymorphic structures.
