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石楠梅纳德、亚历山大斯波科恩和肯德尔霍克教授正在开发黄金化学，将人造聚合物链连接到天然存在的蛋白质和肽上。 合成聚合物与蛋白质和肽的连接在生物分子中产生期望的性质。 这些新型生物材料的应用包括用作具有改善的稳定性或溶解性的治疗剂。 该项目有可能推进商业医疗保健应用的知识。 这项研究的更广泛影响包括增加了拥有化学博士学位的学生人数，特别是女性和代表性不足的少数群体。 其他努力包括通过与洛杉矶布朗尼和少年女童子军部队合作来接触女孩，以及为女童子军制定一个名为好奇心的计划。 已经对STEM感兴趣的女孩通过洛杉矶市长的WiSTEM项目获得指导和网络机会。这项研究的重点是开发合成聚合物-蛋白质结合物的金试剂。 采用理论和实验相结合的方法对有机金（III）试剂进行优化，以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-聚合物缀合物中的用途。 这些反应通过“接枝”和“接枝自”方法合成蛋白质和肽-聚合物缀合物来进行。 此外，非天然氨基酸的遗传编码技术进行检查，将金试剂在蛋白质表面的巯基末端官能化的聚合物进一步修饰。 这项研究有潜力开发新的和高效的合成方法来制备聚合物-蛋白质缀合物。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.