Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan.
Department of Safety, Health and Environmental Engineering, Hungkuang University, Sha Lu, Taichung City 433, Taiwan.
Colloids Surf B Biointerfaces. 2016 Jun 1;142:351-359. doi: 10.1016/j.colsurfb.2016.02.064. Epub 2016 Mar 2.
At least 30 different human proteins can fold abnormally to form the amyloid deposits that are associated with a number of degenerative diseases. The research presented here aimed at understanding the inhibitory potency of a food additive, brilliant blue FCF (BBF), on the amyloid fibril formation of lysozyme. Our results demonstrated that BBF was able to suppress the formation of lysozyme fibrils in a dose-dependent fashion. In addition, the structural features and conformational changes in the lysozyme samples upon the addition of BBF were further characterized using circular dichroism spectroscopy, nile red fluorescence spectroscopy, turbidity assay, and sodium dodecyl sulfate electrophoresis. Through molecular docking and molecular dynamics simulations, BBF's mechanism of action in lysozyme fibrillogenesis inhibition was found to be initiated by binding with the aggregation-prone region of the lysozyme. We believe the results from this research may contribute to the development of effective therapeutics for amyloidoses.
至少 30 种不同的人类蛋白质可以异常折叠，形成与许多退行性疾病相关的淀粉样沉积物。本研究旨在了解一种食品添加剂亮蓝 FCF（BBF）对溶菌酶淀粉样纤维形成的抑制能力。我们的结果表明，BBF 能够以剂量依赖的方式抑制溶菌酶纤维的形成。此外，还使用圆二色性光谱、尼罗红荧光光谱、浊度测定和十二烷基硫酸钠电泳进一步表征了 BBF 加入后溶菌酶样品的结构特征和构象变化。通过分子对接和分子动力学模拟，发现 BBF 在抑制溶菌酶纤维化形成中的作用机制是通过与溶菌酶的聚集倾向区域结合而启动的。我们相信这项研究的结果可能有助于开发有效的淀粉样变性治疗方法。
