Degradable trehalose polymeric materials for protein stabilization

用于稳定蛋白质的可降解海藻糖聚合物材料

• 批准号: 1507735
• 负责人: Heather Maynard
• 金额: $ 48.88万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1507735&HistoricalAwards=false
• 关键词: Degradable; trehalose; polymeric; materials; protein

With this award, the Macromolecular, Supramolecular and Nanochemistry Program of the Division of Chemistry is supporting Professor Heather Maynard at UCLA to conduct research to create polymeric materials that protect proteins to heat, and break down into non-toxic components, to release fully active proteins. Proteins have important biological functions and are useful as tools in scientific research, as reagents in various industries including those that produce chemicals and home care products, as additives to enhance food production, and as therapeutics for a wide variety of diseases. However, for a significant fraction of proteins, instability to heat and other stressing conditions, limits their application. For example, isolated purified proteins often lose activity if stored at room temperature and may be unstable to shipping or storage without refrigeration, increasing costs. As a result, there is interest in polymeric materials that can stabilize proteins to conditions that normally inactivate them, such as changes in temperature. It is also critical for most applications that these materials are degradable, non-toxic, and can release active proteins when and where desired. Through this research, undergraduate and graduate students and postdoctoral researchers will be trained in interdisciplinary research, with a particular effort increase the participation of female and under-represented minorities in chemistry research. In addition, outreach activities are directed at K-12 students from underprivileged and diverse communities, to expose these students.In this research, Maynard's research group will be preparing polymer conjugates and nanoparticles of trehalose glycopolymers that protect proteins, degrade into non-cytotoxic components and release proteins by relevant triggers. Specifically, her group synthesizes and studies end functionalized trehalose glycopolymers that conjugate to proteins, stabilize the biomolecules, and degrade into non-cytotoxic components. The research also aims to prepare degradable trehalose polymer nanoparticles that stabilize and release proteins. This project teaches students valuable synthesis, structure-property relationships with regard to protein stability, and is expected to yield information on cytotoxicity and release of proteins. Since proteins are used in a wide range of practical applications, from the use of antibodies as diagnostics and as therapeutics, to the use of enzymes in the food industry, to the use of proteins as pharmaceutical therapeutic agents, the fundamental discoveries relating to protein stability from this research are expected to impact many different fields.

有了这个奖项，化学部的大分子，超分子和纳米化学计划正在支持加州大学洛杉矶分校的石楠梅纳德教授进行研究，以创造聚合物材料，保护蛋白质加热，并分解成无毒成分，释放完全活性的蛋白质。蛋白质具有重要的生物学功能，并且可用作科学研究中的工具，用作各种工业中的试剂，包括生产化学品和家庭护理产品的工业，用作增强食品生产的添加剂，以及用作各种疾病的治疗剂。然而，对于很大一部分蛋白质，对热和其他应力条件的不稳定性限制了它们的应用。例如，如果在室温下储存，分离的纯化蛋白质通常会失去活性，并且在没有冷藏的情况下运输或储存可能不稳定，从而增加成本。因此，人们对聚合物材料感兴趣，这些材料可以使蛋白质稳定在通常使它们变性的条件下，例如温度的变化。对于大多数应用来说，这些材料是可降解的，无毒的，并且可以在需要的时候和地方释放活性蛋白质，这一点也很关键。 通过这项研究，本科生、研究生和博士后研究人员将接受跨学科研究方面的培训，并将特别努力提高女性和代表性不足的少数群体对化学研究的参与。 此外，Maynard的研究小组还将针对来自贫困和多样化社区的K-12学生开展外展活动，让这些学生接触到这些知识。在这项研究中，Maynard的研究小组将制备海藻糖糖共聚物的聚合物缀合物和纳米颗粒，这些聚合物和纳米颗粒可以保护蛋白质，降解为非细胞毒性成分，并通过相关触发器释放蛋白质。具体来说，她的团队合成和研究末端官能化海藻糖糖共聚物，其与蛋白质缀合，稳定生物分子，并降解为非细胞毒性组分。该研究还旨在制备可降解的海藻糖聚合物纳米颗粒，以稳定和释放蛋白质。该项目教授学生关于蛋白质稳定性的有价值的合成，结构-性质关系，并有望产生关于蛋白质的细胞毒性和释放的信息。由于蛋白质在广泛的实际应用中被使用，从抗体作为诊断和治疗剂的使用，到食品工业中酶的使用，再到蛋白质作为药物治疗剂的使用，这项研究中与蛋白质稳定性有关的基本发现预计将影响许多不同的领域。