4.4 Article

Effect of mono- and diketone group in curcumin analogues on amyloid fibrillation of hen egg white lysozyme

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BIOPHYSICAL CHEMISTRY
卷 292, 期 -, 页码 -

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DOI: 10.1016/j.bpc.2022.106913

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Amyloid fibrillation; Inhibition mechanism; Hen egg white lysozyme

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This study investigated the inhibitory effect of a new mono-ketone-containing curcumin analogue (MDHC) on amyloid fibrillation of hen egg white lysozyme (HEWL). Although MDHC had a lower inhibitory capacity compared to curcumin, it still demonstrated significant inhibitory effect. The findings indicated that the beta-diketone moiety played an important role in the inhibition process of HEWL amyloid fibrillation.
Curcumin has attracted more attention because of its inhibition efficacy on protein amyloid fibrillation. How-ever, the inhibition mechanism was still ambiguous and the clinical application of curcumin was greatly limited because of its poor stability at physiological conditions for the presence of beta-diketone moiety. In this paper, a new mono-ketone-containing curcumin analogue (MDHC) was designed and synthesized to realize the possible in-hibition mechanism and unveil the important role of beta-diketone moiety of curcumin in the inhibition process of amyloid fibrillation using hen egg white lysozyme (HEWL) as model protein. Although all experiment results (ThT, CR, ANS and TEM) showed that the inhibitory capacity of curcumin was better than MDHC, MDHC still could show obvious inhibition effect. Molecular docking showed that both curcumin and MDHC could bind with HEWL by hydrogen bond of phenloic hydroxyl and the binding energy of MDHC was higher than that of cur -cumin. All the findings inferred that beta-diketone group was one of great important groups in the inhibition process of HEWL amyloid fibrillation, which provided more room to construct novel inhibition reagents.

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