SOLID STATE NMR FOR AMYLOID STRUCTURE DETERMINATION

(改编自应用程序)这个项目的目标是产生一个 三种淀粉样蛋白纤维的详细分子模型 AD、B1-40、B1-42和NAC的特点。不同寻常的结构 淀粉样原纤维的特性使其无法用传统方法进行分析 蛋白质结构的测定。该项目使用新的固态硬盘 测量原子间相互作用的核磁共振技术 距离。这些距离可用作限制 可能的结构，使得计算过程可以识别 可能需要进一步测试的候选人。其他技术，例如， 傅里叶变换红外光谱和X射线光纤衍射 分析，将用于实验区分各种 结构模型。在这个项目中确定的模型将被组合 利用原子力获得的有关纤维形态的信息 显微镜研究(项目3)以制作原纤维的工作模型 结构。 除了对分离的淀粉样纤维的研究外，该项目还将 寻求在分子水平上表征与淀粉样蛋白的相互作用 已被发现与淀粉样蛋白结合的化合物的纤维。的信息 这种类型对于淀粉样蛋白结合剂的优化至关重要。是这样的 化合物将是淀粉样蛋白成像设计的关键组成部分 探员们。

(Adapted from the application) The goal of this project is to produce a detailed molecular model of the three amyloid fibrils which are characteristic of AD, B1-40, B1-42 and NAC. The unusual structural properties of amyloid fibrils preclude their analysis by tradition methods of protein structure determination. This project utilizes new solid-state nuclear magnetic resonance (SSNMR) technology to measure interatomic distances. These distances can be used as constraints which limit the possible structures such that a computational procedure can identify likely candidates for further testing. Other techniques, for example, Fourier-transform infrared spectroscopy and x-ray fiber diffraction analysis, will be used experimentally distinguish between various structural models. The model determined in this project will be combined with information about fibril morphology gained from atomic force microscopy studies (Project 3) to produce a working model of fibril structure. In addition to studies of the isolated amyloid fibrils, this project will seek to characterize, at the molecular level, the interaction with amyloid fibrils of compounds which have been found to bind amyloid. Information of this type will be critical for the optimization of amyloid binders. Such compounds will be a critical component of the design of amyloid imaging agents.