Metal-Peptide and Peptide-Peptide Interactions of Relevance to Alzheimer's Disease

与阿尔茨海默病相关的金属-肽和肽-肽相互作用

• 批准号: 106780-2013
• 负责人: Rauk, Arvi
• 金额: $ 3.21万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=593276
• 关键词: Metal; Peptide; Interactions; Relevance; Alzheimer

Alzheimer's disease(AD) is caused by an aggregated form of the amyloid beta peptide (Ab, or Ab(1-42)) in association with metals ions, primarily, Cu2+/Cu1+, Zn2+, Fe3+/Fe2+, ferro- and ferriheme. The overall objective is to determine the chemical causes or propagating steps of AD. The immediate objectives for the next granting period build on previous work and address some important as yet unanswered questions. All are in the realm of basic physical and computational chemistry applied to processes of biological interest. The proposed research directly addresses the structure and redox properties of Cu and Fe(heme)/Ab complexes. These generate reactive oxygen species (ROS) that in bological systems cause damage to cell components. We also address the interactions between Ab and peptides/pseudopeptides, and proteins that bind to it, with the aim of determining binding affinities and sequence specificities. We will also simulate the nature of neuronal and endothelial membranes, and the chemical and physical interactions between them and Ab that result in lipid peroxidation and pore formation.

阿尔茨海默病（AD）是由淀粉样β肽（Ab或Ab（1-42））与金属离子（主要是Cu 2 +/Cu 1+、Zn 2+、Fe 3 +/Fe 2+、亚铁血红素和亚铁血红素）缔合的聚集形式引起的。总体目标是确定AD的化学原因或传播步骤。下一个赠款期的近期目标是在以往工作的基础上制定的，并解决一些尚未得到解答的重要问题。所有这些都是应用于生物学过程的基础物理和计算化学领域。该研究直接涉及Cu和Fe（血红素）/Ab复合物的结构和氧化还原性质。这些产生活性氧物质（ROS），在生物系统中对细胞成分造成损害。我们还解决了抗体和肽/假肽之间的相互作用，并与它结合的蛋白质，以确定结合亲和力和序列特异性的目的。我们还将模拟神经元和内皮细胞膜的性质，以及它们与抗体之间的化学和物理相互作用，导致脂质过氧化和孔形成。