Hexafluoroisopropanol induces self-assembly of ß-amyloid peptides into highly ordered nanostructures

Deposition of insoluble fibrillar aggregates of beta-amyloid (A beta) peptides in the brain is a hallmark of Alzheimer's disease. Apart from forming fibrils, these peptides also exist as soluble aggregates. Fibrillar and a variety of nonfibrillar aggregates of A beta have also been obtained in vitro. Hexafluoroisopropanol (HFIP) has been widely used to dissolve A beta and other amyloidogenic peptides. In this study, we show that the dissolution of A beta 40, 42, and 43 in HFIP followed by drying results in highly ordered aggregates. Although a-helical conformation is observed, it is not stable for prolonged periods. Drying after prolonged incubation of A beta 40, 42, and 43 peptides in HFIP leads to structural transition from a-helical to beta-conformation. The peptides form short fibrous aggregates that further assemble giving rise to highly ordered ring-like structures. A beta 1622, a highly amyloidogenic peptide stretch from A beta, also formed very similar rings when dissolved in HFIP and dried. HFIP could not induce a-helical conformation in A beta 1622, and rings were obtained from freshly dissolved peptide. The rings formed by A beta 40, 42, 43, and A beta 1622 are composed of the peptides in beta-conformation and cause enhancement in thioflavin T fluorescence, suggesting that the molecular architecture of these structures is amyloid-like. Our results clearly indicate that dissolution of A beta 40, 42 and 43 and the amyloidogenic fragment A beta 1622 in HFIP results in the formation of annular amyloid-like structures. Copyright (c) 2012 European Peptide Society and John Wiley & Sons, Ltd.