Amino Acid and Peptide Asssembly: Mechanisms and Structures

氨基酸和肽组装：机制和结构

• 批准号: 1565941
• 负责人: Michael Bowers
• 金额: $ 48万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1565941&HistoricalAwards=false
• 关键词: Amino; Acid; Peptide; Asssembly; Mechanisms

In this project funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Michael T. Bowers at the University of California at Santa Barbara are investigating the mechanism of peptide assembly. Peptide and protein assemblies can contribute to many devastating diseases such as Alzheimer's disease because of amyloid formation. This is an active area of research both for its fundamental importance and its potential impacts on health. Through the studies on model amino acids and peptides, factors that control larger peptide and protein assembly can be learned, which can help the development of new therapeutic agents. The project is well suited for the education of scientists at all levels, including those underrepresented in science. Outreach activities to high school students in the Ventura and Santa Barbara areas are also part of the funded project. A free website that allows the accurate and rapid calculation of cross sections of model structures is also supported by this grant. Specifically, this grant is focused on the assembly of amino acids and small peptides. In these studies, Ion Mobility based Mass Spectrometry (IMS-MS) is used as the main tool. In collaboration with the group of Gert von Helden at the Fritz Haber Institute in Berlin, IMS-MS is coupled with the Fritz Haber free electron laser to do spectroscopy on size and shape selected oligomers of both amino acids and small peptides. The overarching goal is to understand the molecular mechanism of the amyloid cascade that is often observed for peptides and proteins in systems related to many devastating diseases. The amyloid hypothesis states that peptides natively fold and isotropically assemble until at a system dependent size they rearrange to beta sheet and rapidly add monomers to form fibrils. The group, in past NSF support periods, observed this process for specific peptide systems. The current project seeks to understand these observations and to develop an algorithm that can accurately predict the predilection of a peptide or protein to form amyloid knowing only the primary structure.

在这项由化学系化学结构、动态和机制B计划资助的项目中，加州大学圣巴巴拉分校的迈克尔·T·鲍尔斯教授正在研究多肽组装的机制。由于淀粉样蛋白的形成，多肽和蛋白质组合可能导致许多毁灭性的疾病，如阿尔茨海默病。这是一个活跃的研究领域，因为它的基本重要性及其对健康的潜在影响。通过对模型氨基酸和多肽的研究，可以了解控制更大的多肽和蛋白质组装的因素，这将有助于开发新的治疗药物。该项目非常适合各级科学家的教育，包括那些在科学界代表性不足的科学家。针对文图拉和圣巴巴拉地区高中生的外联活动也是资助项目的一部分。这笔赠款还支持一个免费网站，允许准确和快速地计算模型结构的横截面。具体地说，这笔赠款的重点是氨基酸和小肽的组装。在这些研究中，基于离子迁移率的质谱学(IMS-MS)被用作主要工具。IMS-MS与柏林Fritz Haber研究所的Gert von Helden团队合作，将IMS-MS与Fritz Haber自由电子激光相结合，对氨基酸和小肽的选定低聚物进行尺寸和形状的光谱分析。最主要的目标是了解淀粉样级联的分子机制，在与许多毁灭性疾病相关的系统中，经常观察到多肽和蛋白质的淀粉样级联。淀粉样蛋白假说指出，多肽自然折叠和各向同性组装，直到系统决定大小，它们重新排列成β片状，并迅速添加单体形成纤维。在过去的NSF支持期，该小组观察到了特定多肽系统的这一过程。目前的项目试图理解这些观察结果，并开发一种算法，可以准确地预测仅知道一级结构就能形成淀粉样蛋白的多肽或蛋白质的偏好。