Technical: The objectives of this work are to develop linear zwitterionic polymers and investigate their stabilizing effects on proteins. The first task is to synthesize and characterize these zwitterionic polymers. The second task is to study their effects on protein stability and bioactivity using alpha-chymotrypsin as a model protein. The third task is to investigate the effects of conjugating these zwitterionic polymers to interferon-alpha2alpha(INF). Bare INF is rapidly cleared from the body due to its small hydrodynamic radius. Attachment of poly (ethylene glycol) (PEG) to INF increases the in vivo circulation time, but dramatically reduces biological activity. Conjugation with these zwitterions is expected to achieve the same improved stability as PEG, but without sacrificing activity. These tasks will highlight the importance of polymer structure and chemistry on preserving protein stability and bioactivity.
Zwitterionic materials have been shown to stabilize and preserve protein bioactivity while poly(ethylene glycol) (PEG) can stabilize proteins, but compromise their bioactivity. This work will develop a new class of linear zwitterionic materials for a wide range of applications. They are expected to outperform PEG and existing zwitterionic materials. They are particularly suited for conjugation with protein-based therapeutics such as interferon-alpha2alpha (INF), a well-known protein therapeutic used in the treatment of hepatitis C because they can improve protein stability and bioactivity. Graduate, undergraduate, and community college students will be involved in this project, particularly those from underrepresented groups. This project will provide research opportunities for high school students, teachers and visiting scholars. The PI has been actively involved in and will continue to promote international collaborations at national and university levels.
