Gold Reagents for Protein-Polymer Conjugate Synthesis

在这个由化学系大分子、超分子和纳米化学项目资助的项目中，加州大学洛杉矶分校化学和生物化学系的Heather Maynard教授、Alexander Spokoyn教授和Kendall Houk教授正在开发金化学物质，将人工聚合物链附着在自然产生的蛋白质和肽上。将合成聚合物附着在蛋白质和多肽上，在生物分子中产生理想的特性。这些新型生物材料的应用包括用作具有改进的稳定性或溶解度的治疗剂。该项目具有推进商业医疗保健应用知识的潜力。这项研究更广泛的影响包括增加了拥有化学博士学位的学生人数，尤其是女性和代表性不足的少数族裔。其他努力包括通过与洛杉矶布朗尼女童子军和少年女童子军合作，向女孩伸出援手，并为女童子军制定了一个名为“好奇”的项目。已经对STEM感兴趣的女孩可以通过洛杉矶市长的WiSTEM项目获得指导和交流机会。本研究的重点是开发用于合成聚合物-蛋白偶联物的金试剂。采用理论与实验相结合的方法对有机金属金（III）试剂进行优化，了解半胱氨酸芳基化的机理。配体设计扩展了这些操作简单的有机金属试剂在水溶液中合成蛋白质-聚合物偶联物的使用。这些反应是通过“接枝到”和“接枝自”的方法合成蛋白质和肽-聚合物缀合物来进行的。此外，研究了非天然氨基酸遗传编码技术，将金试剂放置在蛋白质表面，以进一步修饰巯基端功能化聚合物。本研究有潜力开发新的高效的合成方法来制备聚合物-蛋白质偶联物。该奖项反映了美国国家科学基金会的法定使命，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。

In this project funded by the Macromolecular, Supramolecular, and Nanochemistry Program in the Division of Chemistry, Professors Heather Maynard, Alexander Spokoyn, and Kendall Houk of the Department of Chemistry and Biochemistry at University of California-Los Angeles are developing gold chemistries to attach the strands of artificial polymers to naturally occurring proteins and peptides. The attachment of synthetic polymers to proteins and peptides create desirable properties in the biomolecules. Applications of these novel biomaterials include use as therapeutic agents with improved stability or solubility. This project has the potential to advance knowledge for commercial healthcare applications. The broader impacts of this research include increasing the number of students, particularly female and underrepresented minorities, with doctoral degrees in chemistry. Other efforts include outreach to girls by working with the Los Angeles Brownie and Junior Girl Scout Troops and the development of a program for Girl Scouts called Curieosity. Girls already interested in STEM are provided with mentorship and networking opportunities through the Mayor of Los Angeles’ program WiSTEM.This research is focused on developing gold reagents to synthesize polymer-protein conjugates. Organometallic gold(III) reagents are optimized using a combination of theory and experiment to understand the mechanism of cysteine arylation. Ligand design expands the use of these operationally-simple organometallic reagents in the synthesis of protein-polymer conjugates in aqueous solutions. These reactions are carried out by synthesizing protein and peptide-polymer conjugates by both “grafting to” and “grafting from” methods. Furthermore, non-native amino acid genetic encoding techniques are examined to place gold reagents at the protein surface for further modification with thiol-end-functionalized polymers. This research has the potential to develop new and highly efficient synthetic methodologies to prepare polymer-protein conjugates.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.