Resveratrol modulates fibrillogenesis in a poly‑l‑lysine peptide

Abstract

Resveratrol (Res) is an effective inhibitor of amyloid fibril formation and reduces neuron cell toxicity. The effect of Res on the fibrillogenesis of a polar polypeptide, poly‑l‑lysine (PLL), was studied by Fourier-transform infrared spectroscopy, vibrational circular dichroism and transmission electron microscopy. Res molecules exhibited strong and specific inhibition of β-sheet-rich fibrils formed by PLL. Side chain-side chain hydrophobic interactions of Lys side chains in aggregated β-sheet structures of PLL stabilize this aggregated state, and this interaction is targeted by Res via hydrophobic interactions. The effect of Res on PLL and other previously reported proteins/peptides sequences with fewer polar amino acids reveals that Res shows rather low sequence specificity. Instead, Res targets sequences that support strong hydrophobic interactions. The fibril-inhibition activity of Res, which is specific toward β-sheet-rich fibrils of proteins/peptides and rather non-specific to the amino acid sequence, indicates that Res is a very promising drug candidate for effective treatment of amyloid-related diseases.