Degradable trehalose polymeric materials for protein stabilization

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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.