β淀粉样多肽聚集抑制剂设计、性能及作用机理研究

项目名称： β淀粉样多肽聚集抑制剂设计、性能及作用机理研究

项目编号： No.51273094

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 一般工业技术

项目作者： 袁直

作者单位： 南开大学

项目金额： 80万元

中文摘要： 阿尔兹海默病是一种最为常见的神经衰退性疾病，其主要病理特征是患者脑内出现由β-淀粉样蛋白（β-amyloid peptide，简称Aβ肽）聚集形成的老年斑。本申请拟针对Aβ肽聚集设计抑制剂，通过多重弱相互作用的协同，达到对Aβ肽的高亲和性、高选择性结合，从而达到抑制其聚集及相关的生理毒性的目的，在此基础上，将有效抑制剂固载到高分子基质上，制备血液灌流用Aβ肽的亲和吸附剂，为重症阿尔兹海默病患者的救治提供另一途径。深入研究抑制剂与Aβ肽的相互作用机理，为抑制剂/吸附剂配体的结构设计提供必要的理论依据。

中文关键词： 阿尔兹海默症；Aβ聚集抑制剂；铜离子；胞内代谢；多重弱相互作用

英文摘要： Alzheimer's disease is the most common neurodegenerative disease.Its main pathological characteristic is the abundant senile plaques formed from amyloid β-peptide (Aβ peptide) in patient's brain.In this application, we intend to design inhibitors for it. Through the synergistical effect of multiple weak interactions, the inhibitors are expected to bind Aβ peptide with high affinity and selectivity, and consequently will decrease the biological toxicity of Aβ peptide. Furthermore, immobilizing the inhibitor to the polymeric matrix, we will obtain Aβ-specific adsorbent for hemoperfusion usage, which could provide another way for the treatment of Alzheimer's disease. Additionally, the interaction mechanism between the inhibitor and the peptide will also be studied, and this is expected to provide basic understand of the principle for the design of inhibitor/adsorbent ligand.

英文关键词： Alzheimer’s disease；Aβ aggregation inhibitor；copper ions；intracellular metabolism；multiple weak interactions