RUI: The Role of Trehalose-Based Oligosaccharides and Glycomacromolecules on Protein Stability

RUI：海藻糖低聚糖和糖大分子对蛋白质稳定性的作用

• 批准号: 1708546
• 负责人: Nicole Snyder
• 金额: $ 29.4万
• 依托单位: Davidson College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1708546&HistoricalAwards=false
• 关键词: RUI; Role; Trehalose; Based; Oligosaccharides

The Chemistry of Life Processes Program in the Chemistry Division funds this research. Professor Nicole L. Snyder of Davidson College investigates a unique carbohydrate, a disaccharide known as trehalose. This research provides a better understanding of the roles of trehalose and trehalose-based analogs in helping organisms survive environmental stresses such as extreme lack of moisture. The experiments use a combination of advanced synthetic and biochemical techniques to systematically study how the structure of trehalose and trehalose-based analogs influence their protective function. The undergraduate students supported by this work receive valuable training in advanced organic synthesis with an emphasis on carbohydrate chemistry, molecular spectroscopy, and biochemical and biophysical techniques that enhances their education and prepares them for a competitive workforce. In addition, this project supports the development of a new course on the emerging subject of Glycomics at Davidson College. An integral part of the project is also a dynamic outreach program that engages the wider community, including local teachers of the Charlotte Teachers Institute, in appreciating the broad role that carbohydrates play in life processes. The unique properties of trehalose and its ability to preserve a wide array of biomolecules under extreme stress (e.g. desiccation, thermal stress, and oxidation) have captured the attention of scientists for over one hundred years. Recently, several novel trehalose-based oligosaccharides (TOS) with unique structures and preservation properties have been identified, but their specific role in molecular preservation is unknown. The fundamental research in this work uses a multifaceted, systematic approach that combines chemical synthesis, molecular spectroscopy and biochemistry to synthesize and analyze a series of novel trehalose-based oligosaccharides (TOS) and trehalose-based precision glycomacromolecules (TPG) to determine how the unique structure of these compounds correlates to their function. Chemical synthesis is used to provide control over the structure of each compound. Once synthesized, each compound is analyzed by NMR spectroscopy to provide detailed structural information. A combination of biophysical studies, including saturation transfer difference (STD)-NMR, differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC), is used to study the solution and solid state associations between TOS/TPG analogs and several proteins selected based on their various stabilities towards desiccation. Finally, enzyme kinetics studies measure the function of enzymes stabilized with TOS/TPG to ensure secondary structure integrity as well as function after desiccation. The results from this research may provide a first look at the factors that govern the structure-function relationships of TOS/TPG and how these unique compounds help organisms survive extreme environmental stress.

化学分部的化学过程计划为这项研究提供了资金。戴维森学院（Davidson College）的妮可·斯奈德（Nicole L.这项研究可以更好地理解海藻糖和基于海藻糖在帮助生物体中生存的环境压力（例如非常缺乏水分）中的作用。该实验结合了晚期合成技术和生化技术的组合来系统地研究海藻糖和基于海藻糖的类似物的结构如何影响其受保护的功能。这项工作支持的本科生接受了高级有机合成的宝贵培训，重点是碳氢化化学，分子光谱以及生化和生物物理技术，从而增强了他们的教育并为竞争性劳动力做好准备。此外，该项目还支持开发有关戴维森学院（Davidson College）糖胶体新兴主题的新课程。该项目不可或缺的一部分也是一个动态的外展计划，该计划吸引了广泛的社区，包括夏洛特教师研究所的当地教师，欣赏碳水合物在生活过程中所发挥的广泛作用。海藻糖的独特特性及其在极端压力下（例如欲望，热应激和氧化）保持多种生物分子的能力，已吸引了一百多年来的科学家的注意。最近，已经鉴定出了几种具有独特结构和保存特性的新型基于海藻糖的寡糖（TOS），但是它们在分子保存中的具体作用尚不清楚。这项工作中的基本研究采用了多方面的系统方法，该方法结合了化学合成，分子光谱和生物化学来合成和分析一系列新型的基于天绿核酸的新型寡糖（TOS）和天杂志精确的精确性精确的糖氯莫洛莫洛莫洛莫洛莫洛梅洛明素（TPG），以确定这些独特的结构，以这些结构为独特的结构。化学合成用于对每种化合物的结构进行控制。合成后，通过NMR光谱分析每种化合物，以提供详细的结构信息。生物物理研究（包括饱和转移差异（STD）-NMR，差异扫描量热法（DSC）和等温滴定量热法（ITC）的结合，用于研究溶液和基于其各种条件选择的TOS/TPG模拟蛋白之间的溶液和固态关联。最后，酶动力学研究测量了用TOS/TPG稳定的酶的功能，以确保二级结构完整性以及欲望之后的功能。这项研究的结果可能会首先研究控制TOS/TPG结构功能关系的因素，以及这些独特化合物如何帮助生物生存在极端的环境压力中。