KINETICS & MECHANISM OF AMYLOID FORMATION STUDIES BY ESR

蛋白质沉积是导致广泛的神经和 全身性疾病，包括传染性海绵状脑病 （TSE）和阿尔茨海默病（AD）。这项研究的目的是 阐明了累积的动力学和机制 朊病毒蛋白（PrPs），这是牵连在TSE，和淀粉样蛋白 (i.e.不溶性纤维蛋白）的形成， 与AD有关 对动力学的理解， 聚集机制将允许合理的治疗策略， 开发用于治疗该疾病。单自旋标记肽， 来自PrP和A β，将由两个人合成和研究。 电子自旋共振（ESR）光谱和电子显微镜（EM） 以确定聚集和淀粉样蛋白形成的动力学。 快速 将为ESR谱仪构建混合系统， 通过溶液混合过程， 并且从有利的聚集开始监测动力学 条件 将制备一系列双自旋标记的肽类似物， 通过ESR进行研究，以确定构象的性质 变更需要汇总。双标记实验 材料还将提供关于 当它作为游离单体存在于溶液中时， 一种聚合状态。 总之，这些实验将有助于 提供了一个完整的事件序列的图片， PrP和A β的聚集和淀粉样蛋白形成。

Protein deposition is responsible for a wide range of neurological and systemic disorders, including transmissible spongiform encephalopathies (TSEs) and Alzheimer's disease (AD). The goal of this research is to elucidate the kinetics and mechanism responsible for the accumulation of prion proteins (PrPs), which are implicated in TSEs, and for amyloid (i.e. insoluble fibrillar protein) formation by the A Beta peptide, which is implicated in AD. An understanding of the kinetics and mechanism of aggregation will allow rational therapeutic strategies to be developed for treatment of the disease. Singly spin labeled peptides, derived from PrP and A Beta, will be synthesized and studied by both electron spin resonance (ESR) spectroscopy and electron microscopy (EM) to determine the kinetics of aggregation and amyloid formation. A rapid mixing system will be constructed for the ESR spectrometer so that amyloid formation can be quickly induced, via a solution mixing process, and the kinetics monitored from the onset of favorable aggregation conditions. A series of doubly spin labeled peptide analogs will be made and studied by ESR to determine the nature of the conformational change required for aggregation. Experiments on the double labeled material will also provide information about the conformation of the peptide when it exists as a free monomer in solution and when it is in an aggregated state. Together, these experiments will assist in providing a complete picture of the sequence of events leading to aggregation and amyloid formation by PrP and A Beta.