Quinopeptide formation associated with the disruptive effect of epigallocatechin-gallate on lysozyme fibrils

Oxidized epigallocatechin gallate inhibited lysozyme fibrillation more strongly than the native form

“…It has been reported that the oxidized form of a polyphenol has a more potent disruptive effect on amyloid fibrils than the reduced form [8], [14]. In previous works [15], [16], we found that the inhibition of lysozyme amyloid fibrillation by polyphenols was associated with the formation of quinoproteins, and that quinone intermediates were actually the active form for phenolic compounds to interrupt amyloid structure.…”

“…The data presented herein suggest that the oxidation of a polyphenol should be considered adequately in its anti-amyloidogenic actions. Recent investigations demonstrated that covalent binding plays an important role in the inhibition of protein fibrillation by EGCG and other polyphenols [15], [16], [21], [43]. Through an auto-oxidation pathway, EGCG transforms to quinone or quinonoid substances which covalently bind to polypeptide chains, resulting in the inhibition of amyloid growth [16], [21], [43].…”

“…Recent investigations demonstrated that covalent binding plays an important role in the inhibition of protein fibrillation by EGCG and other polyphenols [15], [16], [21], [43]. Through an auto-oxidation pathway, EGCG transforms to quinone or quinonoid substances which covalently bind to polypeptide chains, resulting in the inhibition of amyloid growth [16], [21], [43]. Upon incubation of lysozyme with oxidized EGCG, quinoapeptides have been detected (data not shown) by the NBT-staining assay [44], suggesting that the oxidation products are able to transform to quinone or quinonoid substances.…”

“…Lysozyme fibrils were prepared according to previous reports with minor modifications [15], [16]. Briefly, lysozyme was dissolved in HCl solution (10 mM, pH 2.0) containing 150 mM NaCl with or without an inhibitor to a final concentration of 1.0 mg/mL.…”

“…Of the anti-amyloidogenic natural polyphenols, only EGCG is currently being evaluated in the clinic due to its benefits in the treatment of amyloid disorders [17], [18]. Recent in vitro investigations have indicated that EGCG exhibits an inhibitory effect on amyloid formation by β-amyloid peptide, α-synuclein, lysozyme, and other proteins [16], [19], [20], [21], [22]. It has also been reported that the fibril-disrupting efficiency of EGCG is positively correlated with its antioxidant capacity [12], [23].…”