Degradable trehalose polymeric materials for protein stabilization

化学系的大分子、超分子和纳米化学项目获得这一奖项，支持加州大学洛杉矶分校的Heather Maynard教授进行研究，创造出保护蛋白质受热并分解成无毒成分的聚合物材料，以释放完全活性的蛋白质。蛋白质具有重要的生物功能，在科学研究中用作工具，在各种行业中用作试剂，包括生产化学品和家庭护理产品的行业，作为提高食品生产的添加剂，以及作为治疗各种疾病的药物。然而，对于很大一部分蛋白质来说，对热和其他胁迫条件的不稳定性限制了它们的应用。例如，分离纯化的蛋白质如果储存在室温下往往会失去活性，在没有冷藏的情况下可能不适合运输或储存，从而增加了成本。因此，人们对能够将蛋白质稳定到通常使其失活的条件(如温度变化)的聚合物材料感兴趣。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释放活性蛋白质，这一点也是至关重要的。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，特别是努力增加女性和代表性不足的少数群体参与化学研究。此外，外展活动针对来自贫困和不同社区的K-12学生，以暴露这些学生。在这项研究中，梅纳德的研究小组将制备海藻糖聚合物的聚合物结合物和纳米颗粒，这些聚合物保护蛋白质，降解成非细胞毒性成分，并通过相关触发剂释放蛋白质。具体地说，她的团队合成和研究末端功能化的海藻糖糖共聚物，这种聚合物与蛋白质结合，稳定生物分子，并降解为非细胞毒性成分。这项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。这个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，并有望获得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，从使用抗体作为诊断和治疗，到在食品工业中使用酶，再到使用蛋白质作为药物治疗剂，这项研究中关于蛋白质稳定性的基本发现预计将影响许多不同的领域。

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.