ENERGETICS/FOLDING/AMYLOIDOGENESIS--ALZHEIMERS DISEASE

能量/折叠/淀粉样变——阿尔茨海默病

• 批准号: 6499717
• 负责人: JONATHAN P LEE
• 金额: $ 3万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6499717
• 关键词: Alzheimer's disease; acidity /alkalinity; amyloid proteins; conformation; molecular pathology; neuritic plaques; nuclear magnetic resonance spectroscopy; protein folding; protein sequence; temperature

DESCRIPTION: The major focus of this proposal is characterization of the solution conformations of peptides derived from the A-beta protein found in the amyloid plaques associated with Alzheimer's disease. In previous work, Dr. Lee, in collaboration with Dr. John Maggio, has identified a soluble peptide fragment that is both amenable to NMR studies and displays activity in an in vitro plaque-growth assay. He has already determined a solution structure for this fragment and has made 15N relaxation measurements of selected backbone amide groups. In addition, he has found evidence for a pH-dependent conformational change. By studying both the solution conformation and activities of a series of sequence variants, Dr. Lee hopes to establish correlations between conformation and plaque formation. He also plans to carry out detailed molecular dynamics simulations, in collaboration with Dr. John Straub.

描述：该提案的主要重点是表征 从A-beta蛋白中得出的肽的溶液构象 与阿尔茨海默氏病有关的淀粉样斑块。 在以前的工作中 李博士与约翰·马吉奥（John Maggio）博士合作，已经确定 肽片段既适合NMR研究，又显示活性 在体外斑块生长测定中。 他已经确定了解决方案 该碎片的结构，并进行了15N的放松测量 选定的骨干酰胺组。 此外，他还找到了证据 pH依赖性构象变化。 通过研究两个解决方案 李博士希望，一系列序列变体的构象和活动 建立构象与牙菌斑形成之间的相关性。 他 还计划进行详细的分子动力学模拟， 与John Straub博士的合作。

项目成果

Exposing asymmetry between monomers in Alzheimer's amyloid fibrils via reductive alkylation of lysine residues.

通过赖氨酸残基的还原烷基化揭示阿尔茨海默病淀粉样原纤维中单体之间的不对称性。

• DOI: 10.1021/ja015735y
• 发表时间: 2001
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Iwata,K;Eyles,SJ;Lee,JP
• 通讯作者: Lee,JP

Long time dynamic simulations: exploring the folding pathways of an Alzheimer's amyloid Abeta-peptide.

长时间动态模拟：探索阿尔茨海默病淀粉样蛋白 Aβ 肽的折叠途径。

• DOI: 10.1021/ar010031e
• 发表时间: 2002
• 期刊: Accounts of chemical research
• 影响因子: 18.3
• 作者: Straub,JohnE;Guevara,Javier;Huo,Shuanghong;Lee,JonathanP
• 通讯作者: Lee,JonathanP