Linear Zwitterionic Polymers for Protein Conjugation and Preservation

用于蛋白质缀合和保存的线性两性离子聚合物

• 批准号: 1307375
• 负责人: Shaoyi Jiang
• 金额: $ 40万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1307375&HistoricalAwards=false
• 关键词: Linear; Zwitterionic; Polymers; Protein; Conjugation

ID: MPS/DMR/BMAT(7623) 1307375 PI: Jiang, Shaoyi ORG: University of WashingtonTitle: Linear Zwitterionic Polymers for Protein Conjugation and PreservationTechnical: 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.Non-Technical: 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.

ID：MPS/DMR/BMAT（7623）1307375 主要研究者：蒋少毅 ORG：华盛顿大学标题：线性两性离子聚合物用于蛋白质偶联和保存技术：这项工作的目标是开发线性两性离子聚合物，并研究其对蛋白质的稳定作用。 第一个任务是合成和表征这些两性离子聚合物。 第二个任务是以α-糜蛋白酶为模型蛋白，研究它们对蛋白质稳定性和生物活性的影响。 第三个任务是研究这些两性离子聚合物与干扰素-α 2 α（INF）结合的效果。 裸INF由于其小的流体动力学半径而从体内迅速清除。 将聚（乙二醇）（PEG）连接到INF增加了体内循环时间，但显著降低了生物活性。 与这些两性离子的缀合预期实现与PEG相同的改善的稳定性，但不牺牲活性。 这些任务将突出聚合物结构和化学对保持蛋白质稳定性和生物活性的重要性。非技术性：两性离子材料已被证明可以稳定和保持蛋白质的生物活性，而聚乙二醇（PEG）可以稳定蛋白质，但会损害其生物活性。 这项工作将开发一种新的线性两性离子材料的广泛应用。 预计它们的性能将超过PEG和现有的两性离子材料。 它们特别适合与基于蛋白质的治疗剂如干扰素-α 2 α（INF）（一种用于治疗丙型肝炎的众所周知的蛋白质治疗剂）缀合，因为它们可以改善蛋白质稳定性和生物活性。 研究生，本科生和社区学院的学生将参与这个项目，特别是那些来自代表性不足的群体。 该项目将为高中学生、教师和访问学者提供研究机会。 PI一直积极参与并将继续促进国家和大学层面的国际合作。