Confirmation of L-phenylalanine's toxic fibrillary formation and its modulation by D-phenylalanine at different ratios and pH values by using synchrotron FTIR

Abstract

Neurodegenerative diseases such as Alzheimer's and Parkinson's are accompanied by stable needle-like amyloid formation. Tyrosine and phenylalanine, amino acids with aromatic side chains, exhibit a tendency to self-assemble into fibrils in solution. Phenylalanine fibrils form at relatively low concentrations in a layered structure in which layers consist of two rows of phenylalanine molecules connected by hydrogen bonds between the carboxylate and amine groups of neighboring molecules, while the hydrophobic rings are responsible for the interlayer interactions via ?-stacking and cause a decrease in cell viability in a dose-dependent manner. In this study, we demonstrated the vibrational modes responsible for toxic fiber or flake formation in enantiomeric mixtures of D- and L-phenylalanine at different ratios and pH values using synchrotron-FTIR spectroscopy. The results were confirmed by SEM images. © 2025 Elsevier B.V.