中文摘要：

朊蛋白病是一类慢性致死性神经退行性顽疾，其致病机理主要是正常的朊蛋白PrP^C通过构象变换转化为致病型蛋白PrP^Sc，并产生淀粉样沉积和神经毒性．PrP115—135是朊蛋白N-端多肽，具有一定的自聚集性和细胞毒性．为比较钌配合物与不同朊蛋白神经肽的作用机制，本文研究了两个钌配合物四氯钌（III）-咪唑配合物（KP418）和四氯钌（III）-二甲亚砜咪唑配合物（NAMI—A）与PrP115—135的相互作用．结果表明配合物通过静电作用和疏水作用与多肽结合，配合物与PrP115-135的解离常数肠分别为（6．2±1．4）和（6．4±1．1）μmol／L，显示结合性较强．它们对多肽聚集行为也具有良好抑制作用，并有效降低了由该肽引起的细胞毒性，使钌配合物作为多肽聚集抑制剂及潜在的朊蛋白病金属药物成为可能．

英文摘要：

Protein conformational change and amyloid fibrils deposition are associated with severe diseases. Those proteins include amyloid-β protein （Aβ, Alzheimer＇s disease）, human islet amyloid polypeptide （hIAPP, type 2 diabetes mellitus, T2DM）, and prion protein （PrP, transmissible spongiform encephalopathies）. Scientists have focused on studying these amyloid proteins to develop potential drugs against the diseases. Prion disease is a type of chronic progressive fatal neurodegenerative disease, whose pathogenic mechanism is the conformational conversion of normal prion protein PrP^C to a pathogenic type PrP^Sc. The transition produces amyloid deposition and consequent neurotoxicity. PrP115-135 （115-AAAAGAVVGGLGGYMLGSAMS-135） is an N-terminal fragment of PrP with self-aggregation and cytotoxicity. Metal complexes act as traditional antitumor agents, and non-platinum-based metallodrugs are developed to improve clinical effectiveness in terms of their general toxicity and spectral activity. Besides, they interact with various proteins, enzymes and bioactive peptides. Ruthenium complexes can effectively bind to proteins, such as apotransferrin, apolactoferrin, and serum albumin, resulting in the altered protein structure and binding ability toward other molecules. They are also considered as potential inhibitors of amyloid proteins because of their low cytotoxicity and dis- aggregation ability to amyloid fibrils. This work studied the interactions of PrP115-135 with two ruthenium complexes NAMI-A and KP418 in order to compare the action mechanisms between different prion neuropeptides and ruthenium complexes. The intrinsic fluorescence method and cyclic voltammetry （CV） were used to study the binding mode and binding affinity of the two complexes to PrP15-135. In addition, we used Thioflavin T fluorescence assay to display the effects of ruthenium complexes on amyloid peptide aggregation. Furthermore, 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyltetrazolium bromide （MTT） assay was used to reve