Structural characterization of the interaction between the Alzheimer's disease beta-amyloid peptide and the catechin EGCG

绿色茶化合物表没食子儿茶素没食子酸酯（EGCG）抑制阿尔茨海默病β-淀粉样肽（A-β）神经毒性。当ECGG滴定为A-β时，NMR化学位移变化表明单体A-β和EGCG之间的相互作用。低聚物聚集体的存在下形成的表没食子儿茶素产生定义良好的MAS固态NMR光谱，并显示这些沉淀物是可访问的结构分析。该提案的目的是表征从可溶性复合物到聚集态结构的相互作用途径。氧化条件和金属对相互作用的影响将受到严格控制。为此，我们采用溶液状态和MAS固态NMR，以及动态光散射（DLS），小角X射线散射（SAXS），电子显微镜（EM）和原子力显微镜（AFM）的组合。小分子诱导的淀粉样蛋白聚集体的原子结构的知识将有助于合理化的神经毒性的结构基础，并在同一时间打开阿尔茨海默氏病的药物开发的新视角。

The green tea compound epigallocatechin-gallate (EGCG) inhibits Alzheimer's disease beta-amyloid peptide (A-beta) neurotoxicity. Upon titration of ECGG to A-beta, NMR chemical shift changes indicate an interaction between monomeric A-beta and EGCG. Oligomeric aggregates formed in presence of EGCG yield well defined MAS solid-state NMR spectra and show that these precipiates are accessible for a structural analysis. It is the aim of the proposal to characterize the interaction pathway from soluble complexes to the structure in the aggregated state. Oxidative conditions and effect of metals on the interaction will be tightly controlled. For that purpose, we employ a combination of solution-state and MAS solid-state NMR, as well as Dynamic Light Scattering (DLS), Small Angle X-Ray Scattering (SAXS), Electron Microscopy (EM) and Atomic Force Microscopy (AFM). Knowledge of the atomic structure of small molecule induced amyloid aggregates will aid to rationalize the structural basis of neurotoxicity, and at the same time open new perspectives for Alzheimer's disease drug development.