Abstract:
Amyloidoses are a family of diseases characterized by abnormal protein folding that leads to fibril aggregates, amyloids. Extensive research efforts are devoted to developing inhibitors to amyloid aggregates. Here we set to explore functionalized titania (TiO2) nanoparticles (NPs) as potential amyloid inhibiting agents. TiO2 NPs were coated by a catechol derivative, dihydroxy-phenylalanine propanoic acid (DPA), and further conjugated to the amyloids\' specific dye Congo-Red (CR). TiO2-DPA-CR NPs were found to target mature fibrils of β-amyloid (Aβ). Moreover, coated NPs incubated with Aβ proteins suppressed amyloid fibrillation. TiO2-DPA-CR were found to target amyloids in solution and induce their sedimentation upon centrifugation. This work demonstrates the potential utilization of TiO2-DPA NPs for labeling and facilely separating from solution mature amyloid fibrils.
摘要:
淀粉样蛋白是一类以蛋白折叠异常为特征的疾病,导致原纤维聚集体,淀粉样蛋白。广泛的研究工作致力于开发淀粉样蛋白聚集体的抑制剂。在这里,我们开始探索功能化的二氧化钛(TiO2)纳米颗粒(NPs)作为潜在的淀粉样蛋白抑制剂。TiO2NP被邻苯二酚衍生物包覆,二羟基苯丙氨酸丙酸(DPA),并进一步与淀粉样蛋白特异性染料刚果红(CR)缀合。发现TiO2-DPA-CRNP靶向β-淀粉样蛋白(Aβ)的成熟原纤维。此外,与Aβ蛋白一起孵育的包被的NP抑制了淀粉样蛋白纤维化。发现TiO2-DPA-CR靶向溶液中的淀粉样蛋白并在离心时诱导其沉降。这项工作证明了TiO2-DPANP用于标记和从溶液成熟的淀粉样原纤维中轻松分离的潜在用途。