L-ala modified analogues of amyloid β-peptide residue 17-20: self-association and amyloid-like fibril formation

Abstract

L-Ala modified analogues of amyloid β-peptide residue 17-20 LVFF (-L-Leu-L-Val-L-Phe-L-Phe-) have been designed and synthesized to study their self-assembling propensity, the nature of intermolecular interactions and rationalize with short hydrophobic sequences in the middle of Aβ that have important role in the neuropathology of Alzheimer’s disease. The peptides sequences LVFA and LAFA have been adopted from the β-sheet region of non-amyloidogenic proteins (hemoglobin-like falvoprotein and ATP synthase C chain, respectively). All the reported peptides self-associate into amyloid-like fibrils which are readily stained with a physiological dye Congo red and exhibits green gold birefringence under polarized light. The solid state FTIR studies of the fibrils reveal that the reported peptides self-associate through intermolecular hydrogen bonds to form antiparallel β-sheet structure, which is also supported by molecular modeling studies. This result suggests that l-Ala analogous of Aβ17-20, LVFA and LAFA also have virtually identical aggregation behavior.