Polyphenol binding disassembles glycation-modified bovine serum albumin amyloid fibrils.

Glycation of protein results in the formation of advanced glycation end-products (AGEs) and leads to deposition as amyloid fibrils. Adhesive structural properties of polyphenols to aromatic amino acids draw significance in promoting, accelerating and/or stabilizing on-pathway and off-pathway folding intermediates, although the mechanistic action remains unclear. In this study, polyphenols remodeling mature AGEs modified amyloid fibrils were investigated through UV-visible spectroscopy, fluorescence spectroscopy, transmission electron microscopy, atomic force microscopy, circular dichroism spectroscopy, MALDI-MS/MS analysis and molecular docking studies. Our findings confirmed the glycation-mediated transformation of native protein into β-sheet rich amyloid fibrils. SDS-PAGE results suggested the presence of shorter peptide fragments ranging from ~10 kDa to ~40 kDa. MALDI-MS/MS results identified the plausible sequences to be His105-His181, Arg193-Lys242, Leu325-Tyr410, and Ala451-Tyr529. TEM and AFM results suggested that polyphenols binding mature amyloid fibrils remodel/disassemble them into distinct aggregate structures or non-amyloid fibrils. Circular dichroism studies suggested that polyphenols upon binding amyloid fibrils stabilizes and transforms the secondary structure towards helical or random coil-like conformation. Molecular modeling studies suggested high binding affinity and hydrophobic interaction to be the main driving force in remodeling perspective. Together, our findings suggest that polyphenols could differentially remodel mature AGEs-modified amyloid fibrils into distinct aggregate structures through non-covalent interactions and can alleviate AGEs-mediated amyloidosis.