Grafting-from Ring-Opening Metathesis Polymerization from Proteins

蛋白质开环易位聚合接枝

• 批准号: 1808031
• 负责人: Jonathan Pokorski
• 金额: $ 40.96万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1808031&HistoricalAwards=false
• 关键词: Grafting; Ring; Opening; Metathesis; Polymerization

Proteins are the microscopic workhorses of biology and are able to exquisitely perform a wide variety of functions when used in biotechnology. A common problem with proteins though is their poor stability to environmental conditions. Proteins can rapidly lose activity at elevated temperatures or in chemically harsh environments. A common strategy employed to address this issue is to directly attach a polymer to the protein to improve upon stability. Prof. Pokorski and his team at the University of California, San Diego are designing new approaches to streamline the synthesis of protein-polymer hybrids, introduce new function into the polymeric element, and develop methods to modify the protein precisely without impairing its natural function. Furthermore, the team will utilize the research platform to train high school, undergraduate and graduate students to continue to position our nation as a leader in science and technology for future generations.Dr. Pokorski and his team are developing approaches to perform ring-opening metathesis polymerization (ROMP) directly from the surface of a protein macroinitiator. ROMP is challenging under aqueous environments and in complex media that includes proteins. The team aims to optimize grafting-from chemistry in order to precisely control molecular weight, introduce new function to the polymers, and site-specifically label proteins distal to their active sites. The research focuses on three specific aims: 1) optimizing the protein macroinitiator complex to create living polymerization process where molecular weight and dispersity are easily controlled, 2) expand the monomer scope to include zwitterions, oxanorbornenes, and cyclooctene monomers, and 3) site-specifically label proteins and the N- and C-terminus, as well as specific amino acids.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

蛋白质是生物学中的微观工具，在生物技术中使用时能够精细地执行各种各样的功能。 然而，蛋白质的一个共同问题是它们对环境条件的稳定性差。蛋白质在高温下或在化学条件恶劣的环境中会迅速失去活性。 解决这个问题的常用策略是将聚合物直接连接到蛋白质上以提高稳定性。 Pokorski教授和他在加州大学圣地亚哥分校的团队正在设计新的方法来简化蛋白质-聚合物杂交体的合成，将新功能引入聚合物元件，并开发精确修饰蛋白质而不损害其天然功能的方法。此外，该团队还将利用该研究平台培养高中生、本科生和研究生，为子孙后代继续将我国定位为科学技术的领导者。Pokorski博士及其团队正在开发直接从蛋白质大分子引发剂表面进行开环易位聚合（ROMP）的方法。ROMP在水性环境和包括蛋白质的复杂介质中具有挑战性。 该团队的目标是优化接枝化学，以精确控制分子量，为聚合物引入新功能，并在其活性位点远端特异性标记蛋白质。该研究侧重于三个具体目标：1）优化蛋白质大分子引发剂复合物以产生活性聚合方法，其中分子量和分散性容易控制，2）扩大单体范围以包括两性离子、氧杂降冰片烯和环辛烯单体，和3）位点特异性标记蛋白质和N-和C-末端，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。