In this project funded by the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry, Heather Maynard of the University of California at Los Angeles will synthesize and study trehalose-containing polymers for the stabilization of proteins to environmental stressors and proteolytic degradation. Protein-reactive trehalose side chain monomers and polymers will be synthesized using controlled radical polymerization techniques. These polymers will be conjugated to proteins, and the stabilization of the proteins by the glycopolymers will be quantified. The broader impacts of the project involve training undergraduate and graduate students, educating kindergarten through high school girls about chemistry, polymers, and biomolecules through partnership with the Girl Scouts of Los Angeles, and participating in outreach to the general public via UCLA Parents Weekend and UCLA Alumni Day.
Proteins are important reagents in chemical and pharmaceutical industry; however, many proteins are unstable and require specialized conditions such as cold temperatures during storage, transport, and use. Proteins that are attached to trehalose polymers are expected to have significantly increased lifetimes and bioactivities compared to unmodified versions. This research is expected to significantly broaden the use of proteins by academic researchers and industry by reducing the costs of storage and transportation, and it should also enable the use of proteins where storage would be difficult or impossible. This work will contribute to the synthesis of active and stable proteins for a wide range of applications and could impact the polymer, chemical, biomedical and materials communities.
Proteins are used to make chemicals and are in animal feed, cosmetics, personal care products, and drugs to treat conditions such as diabetes and cancer. Unfortunately, most proteins are unstable. If they are taken out of the refrigerator or freezer they degrade and no longer function properly (Figure 1a). To prevent this from happening, these products (especially medicines) require specialized storage and transport such as refrigerated trucks and frozen storage. This significantly increases costs, inconvenience, and limits use of these products. In this research, polymers were developed that when added or attached to proteins protect them from stresses that occur during changes in temperature or removal of water. The polymers, called PolyProtek, are based on a natural sugar used by organisms in the desert to help them survive without rain for long periods of time. PolyProtek was shown to keep proteins stable to very hot temperatures (Figure 1b), during complete removal of water and upon exposure to radiation. The research developed as a result of this funding had a positive impact on the plastics, chemistry, biomedical and materials communities by providing ways to mimic natural sugars and stabilize proteins. This funding also had a major impact on training of students for the next generation workforce. Thirteen students were involved in this project, including five female and underrepresented minority students. Two postdoctoral researchers are now assistant professors, four graduate students obtained their doctoral degrees and have gone on to positions in academia and industry, and two undergraduates are applying to medical schools. In addition, outreach to the Girl Scouts of Los Angeles enabled K-12 girls to learn about chemistry and proteins. The research was also disseminated broadly through laboratory tours and talks to K-12 students, undergraduates and community college students in the local Los Angeles area. This outreach promoted excitement about science, chemistry and research in general; it was gratifying to see young people learn about the possibilities of making a positive difference as scientists. Many of these students are from underrepresented or underprivileged groups. Thus, this research had tremendous impact on the broader and diverse community.