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A Small-Angle Scattering Study of the Self-Assembly of Amyloid Peptide Fragments and Copolymers

淀粉样肽片段和共聚物自组装的小角散射研究

基本信息

批准号：
EP/G067538/1
负责人：
Ian Hamley
金额：
$ 18.27万
依托单位：
University of Reading
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2010
资助国家：
英国
起止时间：
2010 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FG067538%2F1
关键词：
Small Angle Scattering Study Self

项目摘要

The mechanisms and kinetics of fibrillisation of fragments of the amyloid peptide responsible for diseases such as Alzheimers and type II diabetes will be investigated. We will perform time-resolved x-ray scattering at the new Diamond synchrotron in order to probe the growth processes of fibrils produced by short (5-7 amino acid) fragments of the amyloid beta peptide. The sequences selected have been shown to be critical in fibrillisation. We will also investigate the self-assembly of copolymers of the peptide with poly(ethylene glycol), PEG. PEG is a water soluble polymer that has been approved for pharmaceutical applications. The PEG will be attached to peptide fragments designed to bind to the full disease-causing peptide. We expect it will provide steric stability to peptide fibrils, forming a coating layer that prevents aggregation into larger aggregates as observed as a symptom of amyloid disease. We will study the mechanisms and kinetics of self-assembly of the amyloid peptide and peptide polymer fibrils to gain insights into how fibrillisation occurs in the peptide sequences and how it can be prevented using PEG copolymers. In addition, we will examine the effects of solvent, salt and pH on the aggregation process, for instance ensuring that we investigate fibrillisation under physiological conditions of pH and salt. The small-angle x-ray scattering data will be analysed to determine the size and shape of the peptide aggregates. The formation of liquid crystal phases at high concentrations will be investigated, as will shear flow alignment, relevant to flow encountered in the bloodstream. These will involve state-of-the-art simultaneous x-ray scattering and shear viscosity measurements.

淀粉样肽片段纤化的机制和动力学将被研究，这些片段会导致阿尔茨海默病和II型糖尿病等疾病。我们将在新的金刚石同步加速器上进行时间分辨x射线散射，以探测淀粉样蛋白β肽短片段（5-7个氨基酸）产生的原纤维的生长过程。所选择的序列已被证明是纤颤的关键。我们还将研究多肽与聚乙二醇共聚物的自组装。聚乙二醇是一种水溶性聚合物，已被批准用于制药应用。聚乙二醇将被附着在肽片段上，旨在与完整的致病肽结合。我们预计它将为肽原纤维提供空间稳定性，形成一层涂层，防止聚集成更大的聚集体，这是淀粉样蛋白疾病的症状。我们将研究淀粉样肽和肽聚合物原纤维的自组装机制和动力学，以深入了解肽序列中纤化是如何发生的，以及如何使用PEG共聚物来防止纤化。此外，我们将研究溶剂、盐和pH值对聚集过程的影响，例如确保我们在pH和盐的生理条件下研究纤原化。将分析小角度x射线散射数据，以确定肽聚集体的大小和形状。将研究高浓度下液晶相的形成，以及与血流中遇到的流动相关的剪切流排列。这将包括最先进的同时x射线散射和剪切粘度测量。