Polyphenols redirects the self-assembly of serum albumin into hybrid nanostructures

Abstract

Chronic hyperglycemia results in the formation of advanced glycation end-products (AGEs) and triggers amyloid fibril formation. Molecules designed to inhibit amyloid fibrils function by eliminating toxic oligomers or reducing fibril formation. Here, the bioactivity of polyphenols in redirecting the self-assembly of amyloid fibrils was reported through microscopic, spectroscopic and molecular docking studies. Our findings illustrate that glycation causes BSA to self-assemble into amyloid fibrils. 17 Lys residues had modified to carboxy methyl lysine (CML) but only Lys523 was probable of modifying into carboxy ethyl lysine (CEL). In contrast, only 6 Arg residues are identified to be modified to Argpyrimidine (Arg-p). A simple polyphenol baicalein (BLN) redirect the self-assembly of amyloid fibrils into off-pathway hybrid nanostructures. Circular dichroism spectroscopic studies suggested that in the presence of BLN helical conformation was favored. Molecular modeling studies suggested that hydrogen bonding and hydrophobic interaction of polyphenols preferentially at crucial amyloidogenic regions can hinder amyloid fibrillation (Phe133, Lys136, Tyr137, Ile141, Tyr160 and Arg185). Mass spectrometric results illustrated that the presence of a simple polyphenol BLN several residues are unmodified to CML, CEL or Arg-p. Together, our findings suggest that polyphenols could have a protective effect and the redirection can help alleviate the amyloid fibril formation.