项目名称: 金属配合物与朊蛋白神经肽的相互作用
项目编号: No.21271185
项目类型: 面上项目
立项/批准年度: 2013
项目学科: 数理科学和化学
项目作者: 杜为红
作者单位: 中国人民大学
项目金额: 80万元
中文摘要: 朊病毒病是由蛋白构象变化引起的一类神经退行性疾病,该病发病率不断增加,但尚无有效治疗方法。朊病毒病的发生被认为与致病型朊蛋白PrPSc的聚集有关, 因而寻求能有效抑制朊蛋白聚集的金属药物是治疗朊病毒病的重要研发思路。人朊蛋白神经肽 PrP106-126与致病型朊蛋白PrPSc具有相似的理化性质和生物活性,是研究朊蛋白的理想模型。前期工作中我们发现一些金属配合物与PrP106-126有较好的结合作用并有效抑制了神经肽的聚集,但是配体性质、配体构型如何影响金属配合物与神经肽PrP106-126的结合机制及抑制聚集机理还不清楚。本课题拟通过多种谱学手段研究不同配体的金属配合物与PrP106-126及其突变体的相互作用,探索配体构型和关键氨基酸对金属配合物-神经肽结合作用及神经肽聚集性质的影响,揭示金属配合物与朊蛋白神经肽的结合方式及抑制多肽聚集的作用机制,该研究对发展潜在金属药物具有重要意义。
中文关键词: 金属配合物;朊蛋白神经肽;聚集;配体性质;相互作用
英文摘要: Prion disease is a kind of neurodegenetive disorder, which is induced by the conformational change of prion protein. With the increasing of the incidence, this disease seriously influences human being's health, and no effective therapeutics are found out until now. The nosogenesis of prion disease is thought to be ralative with the aggregation of an aberrant conformational isomer of prion protein, PrPSc. Hence, it will be an important pathway of drug design to explore the effective chemical compounds that inhibit protein aggregation. The human prion neuropeptide PrP106-126, has similar physiological characteristics and bioactivities with aberrant prion protein PrPSc, which is an ideal model to invesitigate the structural and functional relationship of prion protein. In our former work, some metal complexes were revealed to well interact with PrP106-126 and inhibit the aggeragation of this neuropeptide. However, it is still unclear that how the ligands property and their configurations affact the binding affinity and aggregation between metal complexes and PrP106-126. In the present project, some mothods including NMR, ESI-MS and fluorescence spectrometry will be used to investigate the interaction between different metal complexes and PrP126-126 as well as its mutants. The effects of ligand property and key res
英文关键词: Metal complexes;Prion protein neuropeptide;Aggregation;ligand property;Interaction