A Novel Glycopolymer to Enhance Protein Stability

Proteins have found utility for numerous commercial and clinical purposes, including use in biochemical and chemical processes, and as agents for the treatment and prevention of human and veterinary disease. A major challenge associated with the use of proteins is their inherent instability. Many proteins rapidly degrade in response to "environmental stresses," such as changes in temperature, pH, light, and desiccation, which has implications for their production, transport, use and storage. Attachment of poly(ethylene glycol) to therapeutic proteins, a process commonly referred to as PEGylation, has been used successfully to increase their stability in vivo by reducing both protease degradation and renal clearance. However, PEGylation does not necessarily increase protein stability in response to environmental stresses. The development of a technology that enhances the stability of proteins to such stresses would dramatically increase the number of proteins that could be used commercially, reduce costs associated with protein production, storage and transportation, and increase protein shelf-life.

Dr. Heather Maynard and colleagues at UCLA have developed a novel glycopolymer to enhance the stabilization of proteins in response to various environmental stressors, including lyophilization and heat. The glycopolymer incorporates the disaccharide trehalose, which is frequently used as a preservative in foods and is Generally Regarded As Safe. The trehalose-based polymer developed by the Maynard group is prepared in such a way to have end-groups that the polymer can, if desired, be directly attached to the biomolecule. Direct attachment of the trehalose-polymer to proteins increases protein stability using lower polymer concentrations. Moreover, the method of synthesis allows for the preparation of trehalose-based polymers with a narrow molecular weight distribution, something that has not been achievable using methodologies developed by others. Studies are underway to determine whether the attachment of the trehalose-based polymer to the biomolecule also confers properties that are similar or superior to PEGylation, such as enhanced protection from proteolytic degradation and extended in vivo circulation time