Synthesis of Polymer-Protein Hybrid Materials Using Site Selective Protein Modification Reactions

在这个由化学部门的大分子、超分子和纳米化学项目资助的项目中，加州大学伯克利分校的马修·弗朗西斯将开发一种可扩展的n端转氨反应，作为在单个位置用单个官能团修饰蛋白质的一种手段，并演示该方法在制备用于水净化的蛋白质-聚合物混合物中的应用。这个项目的方法包括两个部分。首先，PI最近开发的n端化学修饰反应将用于将具有较低临界溶液温度（LCST）的聚合物附着在能够隔离重金属、锕系元素或激素的蛋白质上。将研究这些蛋白质-聚合物混合物去除水中微量这些污染物的功效。其次，基于母体转胺化学收率的提高，通过奎宁缩聚捕获亚胺，或对Claisen缩聚的适应，将开发新的低成本，高效的转胺试剂。人们认为，这些方法将提高蛋白质修饰化学的可扩展性，从而促进这些蛋白质-聚合物系统的制造和创新。更广泛的影响包括培训研究生和本科生，通过在扶轮社会议和其他此类地方组织的演讲向成人学习者推广，创建新的“厨房化学”课程，以及针对和去除水中特定杂质的方法的潜在社会效益。这项工作所开发的新技术将为在特定位置修饰生物分子提供许多途径。这些修饰蛋白可用于各种生物技术应用，包括用于去除饮用水中的重金属离子、锕系金属和有机毒素的低成本试剂。

In this project funded by the Macromolecular, Supramolecular and Nanochemistry Program of the Chemistry Division, Matthew Francis of the University of California at Berkeley will develop a scalable N-terminal transamination reaction as a means to modify proteins with a single functional group at a single location and to demonstrate the use of this methodology in the preparation of protein-polymer hybrids for water purification. The approach to the project involves two parts. First, the PI's recently developed N-terminal chemical modification reaction will be used to attach polymers that exhibit a lower critical solution temperature (LCST) to proteins capable of sequestering heavy metals, actinides or hormones. The efficacy of these protein-polymer hybrids in removing trace amounts of these contaminants from water will be studied. Second, new low-cost, efficient transamination reagents will be developed based upon yield improvement of the parent transamination chemistry, imine capture via quinine condensation, or adaptations of the Claisen condensation. It is thought that such methods will improve the scalability of the protein modification chemistry and thereby facilitate manufacturing and innovation with these protein-polymer systems. The broader impacts involve training graduate and undergraduate students, outreach to adult learners through presentations at Rotary Club meetings and other such local organizations, creating a new "Chemistry in the Kitchen" class, and the potential societal benefits of methodologies to target and remove specific impurities from water.The new techniques developed in this work will provide many avenues for the modification of biomolecules in specific locations. These modified proteins could be used in a variety of biotechnology applications including low cost agents for the removal of heavy metal ions, actinide metals, and organic toxins from drinking water.