TREHALOSE GLYCOPOLYMERS FOR USE IN PROTEIN STABILIZATION
Marco Messina, Jeong Hoon Ko, Emma Pelegri-O'Day, Heather Maynard.
University of California, Los Angeles, Los Angeles, CA.
Proteins play important roles as laboratory reagents and therapeutics for many different diseases. However, proteins are inherently unstable and are prone to degradation by various stressors such as heat, desiccation, and light. Trehalose, a nonreducing disaccharide, has proven to be an effective stabilizer for proteins. Previous work in our lab has demonstrated that trehalose glycopolymers can stabilize proteins against heat and lyophilization better than trehalose as excipients and as protein conjugates. In this study, we synthesized 3 trehalose monomers substituted with styrenyl ether moieties at the C2, C4, and C6 position. Three 8 kDa polymers were synthesized using each monomer separately and one polymer using all of the monomers via free radical polymerization with azobisisobutyronitrile (AIBN) as an initiator. The protein lysozyme was stressed at 90 °C for 20 minutes and β-galactosidase was lyophilized for 3 cycles in the presence of various weight equivalences of each polymer. The glycopolymer containing the C2 regioisomer outperformed the other regioisomers against heat at 25 weight equivalents heat and against lypophilization at 10 weight equivalents. These results suggest that trehalose glycopolymers are promising excipients for the stabilization of proteins against stressors and afforded us valuable insight into the effect polymers decorated with monomers of differing regiochemistry have on the stabilization of proteins. We are currently investigating the ability of these polymers to stabilize monoclonal antibodies and vaccines against heat stress.