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

化学系的生命过程化学项目资助了这项研究。Nicole L.教授戴维森学院的斯奈德研究了一种独特的碳水化合物，一种被称为海藻糖的二糖。 这项研究提供了一个更好的了解海藻糖和海藻糖为基础的类似物在帮助生物体生存的环境压力，如极端缺乏水分的作用。这些实验结合了先进的合成和生物化学技术，系统地研究了海藻糖和海藻糖类似物的结构如何影响其保护功能。由这项工作支持的本科生在高级有机合成方面接受了宝贵的培训，重点是碳水化合物化学，分子光谱学以及生物化学和生物物理技术，这些技术可以提高他们的教育水平，并为具有竞争力的劳动力做好准备。此外，该项目还支持戴维森学院开发一门关于糖组学这一新兴学科的新课程。该项目的一个组成部分也是一个动态的外展计划，使更广泛的社区，包括夏洛特教师学院的当地教师，在欣赏碳水化合物在生命过程中发挥的广泛作用。海藻糖的独特性质及其在极端应力（例如干燥、热应力和氧化）下保存多种生物分子的能力已经吸引了科学家一百多年的注意力。近年来，人们发现了几种结构和防腐性能独特的新型海藻糖基寡糖，但其在分子防腐中的具体作用尚不清楚。这项工作的基础研究采用了多方面的系统方法，结合化学合成，分子光谱学和生物化学，合成和分析了一系列新型海藻糖基寡糖（TOS）和海藻糖基精密糖大分子（TPG），以确定这些化合物的独特结构与其功能的关系。化学合成用于控制每种化合物的结构。一旦合成，每个化合物通过NMR光谱分析，以提供详细的结构信息。结合的生物物理研究，包括饱和转移差（STD）-NMR，差示扫描量热法（DSC），和等温滴定量热法（ITC），是用来研究TOS/TPG类似物和几种蛋白质之间的溶液和固态协会选择的基础上，他们对干燥的各种稳定性。最后，酶动力学研究测量用TOS/TPG稳定的酶的功能，以确保二级结构完整性以及干燥后的功能。这项研究的结果可能会提供第一次看到的因素，支配TOS/TPG的结构-功能关系，以及这些独特的化合物如何帮助生物体生存极端的环境压力。

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.