Impact on the replacement of Phe by Trp in a short fragment of Aβ amyloid peptide on the formation of fibrils

A beta(16-22) (Ac-KLVFFAE-NH2) is one of the shortest amyloid fibril-forming sequences identified in beta-amyloid peptide. At neutral pH, the peptide forms fibrils in the concentration range of 0.2-2.0mM after >= 10 days of incubation. Structures of the fibrils proposed based on solid-state NMR and MD simulations studies suggest antiparallel arrangement of beta-strands and aromatic interactions between the Phe residues. In an effort to examine the role of aromatic interactions between two Phe residues in A beta(16-22), we have studied the self-assembly of A beta(16-22) (A beta FF) and two of its variants, Ac-KLVFWAE-NH2 (A beta FW) and Ac-KLVWFAE-NH2 (A beta WF). The peptides were dissolved in methanol (MeOH) at a concentration of 1 mM and in water (A beta FW and A beta WF, 1mM; A beta FF, 330 mu M). Peptide solutions (100 mu M) were prepared in 50 mM sodium phosphate buffer at pH 7 by diluting from MeOH and water stock solutions. A beta FW forms amyloid-like fibrils immediately from MeOH, as indicated by atomic force microscopy. Dilution of A beta FW into phosphate buffer from stock solution prepared in MeOH results in fibrils, but with different morphology and dimensions. The secondary structure potentiated by MeOH seems to be important for the self-assembly of A beta FW, as fibrils are not formed from water where the peptide is unordered. On the other hand, A beta FF and A beta WF do not form amyloid fibrils rapidly from any of the solvents used for dissolution. However, drying of A beta WF from MeOH on mica surface gives rod-like and fibrous structures. Our study indicates that positioning of the aromatic residues F and W has an important role to play in promoting self-assembly of the A beta(16-22) peptides. Copyright (C) 2010 European Peptide Society and John Wiley & Sons, Ltd.