Department of Mechanical Engineering, Dr. MGR Educational and Research Institute, Maduravoyal, Chennai, 600095, India.
Department of Chemistry, National Institute of Technology, Tiruchirappalli, 620015, India.
Eur Biophys J. 2021 Dec;50(8):1069-1081. doi: 10.1007/s00249-021-01566-w. Epub 2021 Aug 29.
The sensitivity of protein molecular structures makes them susceptible to aggregation in conditions unfavorable for the maintenance of their native folds. The aggregation of proteins leads to many disorders, but the inhibition of amyloid fibril formation using metal-containing small molecules is gaining popularity. Herein we report the effect of nickel(II) complexes (N1, N2, N3, and N4) bearing thiosemicarbazones on the inhibition of amyloid fibril formation by insulin. The interactions of the complexes with amyloid fibrils were investigated using various biophysical techniques, including light scattering, intrinsic fluorescence assay, thioflavin T (ThT) assay, and Fourier transform-infrared spectroscopy. The results revealed that the phenyl-substituted N3 was an efficient inhibitor of amyloid fibril formation and maintained the insulin in its native structure despite conditions promoting fibrillation. Nickel(II) complexes containing indole based thiosemicarbazones were efficient in inhibiting the amyloid fibril formation and maintaining the insulin in its native structure in unfavorable conditions.
蛋白质分子结构的敏感性使它们容易在不利于维持其天然折叠的条件下聚集。蛋白质的聚集会导致许多疾病，但使用含金属的小分子抑制淀粉样纤维形成正变得越来越受欢迎。本文报道了含噻唑烷酮的镍（II）配合物（N1、N2、N3 和 N4）对胰岛素抑制淀粉样纤维形成的影响。使用各种生物物理技术，包括光散射、内源荧光测定、硫黄素 T（ThT）测定和傅里叶变换红外光谱，研究了配合物与淀粉样纤维的相互作用。结果表明，苯基取代的 N3 是一种有效的淀粉样纤维形成抑制剂，尽管有促进纤维形成的条件存在，但它能使胰岛素保持其天然结构。含吲哚基噻唑烷酮的镍（II）配合物能有效抑制淀粉样纤维的形成，并在不利条件下使胰岛素保持其天然结构。
