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金属依赖性抑制淀粉样纤维形成:钴-鞣酸网络的协同效应。

Metal-dependent inhibition of amyloid fibril formation: synergistic effects of cobalt-tannic acid networks.

机构信息

ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.

出版信息

Nanoscale. 2019 Jan 23;11(4):1921-1928. doi: 10.1039/c8nr09221d.

Abstract

Metal-phenolic networks (MPNs) have received widespread interest owing to their modular incorporation of functional metal ions and phenolic ligands. However, the interaction between MPNs and biomolecules is still relatively unexplored. Herein, we studied the effects of MPN-coated gold nanoparticles on amyloid fibril formation (which is associated with Alzheimer's disease) as a function of the metal ion in the MPN systems. All coated particles examined inhibited amyloid formation, with cobalt(ii) MPN-coated particles exhibiting the highest inhibition activity (90%). Molecular dynamics simulations and quantum mechanics calculations suggested that the geometry of the exposed cobalt coordination site in the cobalt-tannic acid networks facilitates its interactions with histidine and methionine residues in the amyloid beta peptides. Furthermore, the unique structure of cobalt MPNs may enable a wider variety of biomedical applications.

摘要

金属-酚醛网络(MPNs)因其可模块化地纳入功能性金属离子和酚配体而受到广泛关注。然而,MPNs 与生物分子之间的相互作用仍相对未知。在此,我们研究了 MPN 包覆的金纳米粒子对淀粉样纤维形成(与阿尔茨海默病有关)的影响,这是作为 MPN 系统中金属离子的函数。所有被研究的包覆粒子都抑制了淀粉样纤维的形成,其中钴(ii)MPN 包覆的粒子表现出最高的抑制活性(90%)。分子动力学模拟和量子力学计算表明,在钴-鞣酸网络中暴露的钴配位位点的几何形状有利于其与淀粉样β肽中的组氨酸和甲硫氨酸残基相互作用。此外,钴 MPN 的独特结构可能使其能够应用于更多种类的生物医学领域。

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