Copper-peptide Chemistry; Alzheimer's Disease Relevance

铜肽化学；

• 批准号: 7085506
• 负责人: RICHARD A HIMES
• 金额: $ 4.45万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-15 至 2008-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7085506
• 关键词: Alzheimer' s disease; aminoacid; amyloid proteins; chemical synthesis; copper; electrochemistry; high performance liquid chromatography; histidine; hydrogen peroxide; intermolecular interaction; metal complex; metalloenzyme; neurochemistry; nuclear magnetic resonance spectroscopy; oxidative stress; peptides; protein sequence; sulfur

DESCRIPTION (provided by applicant): Novel copper-peptide complexes based on fragments of the amyloid beta peptide, implicated in the pathogenesis of Alzheimer's Disease, will be studied structurally and chemically. The purposes of these studies are to elucidate the role of several amino acid sequence motifs of interest found in the A-beta peptide as well as such biologically important metalloenzymes as cytochrome c oxidase, petidylglycine alpha-hydroxylating monoxygenase, and dopamine beta-hydroxygenase. The research will potentially shed light on the role of the sequences of interest on binding copper, determining structure, and activating copper for biological function in these metalloenzymes. In addition, the studies address the roles of copperdioxygen reactivity and copper-peptide interactions in the oxidative stress associated with Alzheimer's Disease and experimentally linked at A-beta. This will be accomplished by structural characterization of copper-peptide complexes in the +1 and +2 oxidation states, as well as reactivity and mechanistic studies of Cu(l) chemistry with dioxygen and hydrogen peroxide.

描述（由申请人提供）： 将对基于淀粉样β肽片段的新型铜肽复合物进行结构和化学研究，该肽与阿尔茨海默氏病的发病机制有关。这些研究的目的是阐明 A-β 肽中发现的几个感兴趣的氨基酸序列基序以及生物学上重要的金属酶（如细胞色素 c 氧化酶、哌啶甘氨酸 α-羟化单加氧酶和多巴胺 β-羟合酶）的作用。该研究将有可能揭示感兴趣的序列在这些金属酶中结合铜、确定结构和激活铜的生物功能方面的作用。此外，这些研究还探讨了铜二氧反应性和铜-肽相互作用在与阿尔茨海默病相关的氧化应激中的作用，并通过实验与 A-β 相关。这将通过 +1 和 +2 氧化态铜肽复合物的结构表征以及 Cu(I) 与分子氧和过氧化氢化学反应的反应性和机理研究来完成。