DNA-Scaffolded Peptides as High-Affinity Reagents

非技术性：这项由佐治亚大学材料研究部生物材料项目授予佐治亚大学的奖项是通过在单链DNA上支架多肽来开发抗体模拟平台。该奖项由生物科学局分子和细胞生物科学部的遗传机制项目共同资助。抗体对于促进生物医学研究中的发现是必不可少的；然而，它们有各种缺点，引起了人们对生物医学研究中获得高质量抗体的关注。为了推动发现工作向前发展，需要用于分子识别的替代和更坚固的聚合物。核酸聚合物已显示出作为高亲和力试剂的巨大前景；然而，它们缺乏化学功能，限制了它们作为受体与蛋白质竞争的能力。通过融合具有不同蛋白质功能的核酸聚合物的可进化分子支架，PI旨在为生物医学研究进化出一类新的抗体模拟物，这可能解决可用于分子靶标的抗体的关键缺陷。这些研究工作将与高中、本科和研究生层面的教育和培训外展相结合，以帮助培养具备适当装备来解决跨学科研究问题的下一代科学家。技术：这项建议描述了通过在DNA上支架多肽来开发抗体模拟的体外选择平台的研究。与传统抗体相比，核酸适配子具有许多优点；然而，它们的官能团缺陷限制了它们与蛋白原亲和试剂的性能相匹配的潜力。通过将核酸聚合物的可进化分子支架与蛋白质功能相结合，这位研究人员将使用这类聚合物来模拟自然界在蛋白质-蛋白质界面上使用的异价和多价方法。研究人员将使用一种酶策略来测序--特别是沿着DNA模板整合独特的多肽片段。这一方法将使单链DNA支架的同时进化和所展示的多肽的鉴定实现对蛋白质靶标的分子识别。如果成功，这种新型仿生聚合物将有助于解决生物医学研究中高亲和力试剂的不足。这些研究工作将与高中、本科生和研究生层面的教育和培训外展相结合。

Non-technical: This award by the Biomaterials program in the Division of Materials Research to University of Georgia is to develop a platform for antibody mimetics by scaffolding peptides on single stranded DNA. This award is cofunded by the Genetic Mechanisms program in the Division of Molecular & Cellular Biosciences in the Directorate for Biological Sciences. Antibodies are essential to facilitating discoveries in biomedical research; however, they have a variety of shortcomings that have elicited concerns over accessibility to high-quality antibodies for biomedical research. Alterative and more robust polymers for molecular recognition are needed to drive discovery efforts forward. Nucleic acid polymers have demonstrated immense promise as high-affinity reagents; however, their lack of chemical functionality limits their ability to compete with proteins as receptors. By merging the evolvable molecular scaffold of nucleic acid polymers with diverse protein functionality, the PI aims to evolve a new class of antibody mimetics for biomedical research, which may address the critical deficit of available antibodies for molecular targets. These research efforts will be coupled with educational and training outreach at the high school, undergraduate, and graduate levels in order to assist in the development of a future generation of scientists that are properly equipped to tackle interdisciplinary research problems.Technical: This proposal describes research to develop an in vitro selection platform for antibody mimetics by scaffolding peptides on DNA. Nucleic acid aptamers have provided numerous advantages over traditional antibodies; however, their functional group deficit limits their potential to match the performance of proteinogenic affinity reagents. By merging the evolvable molecular scaffold of nucleic acid polymers with protein functionality, this investigator will use this class of polymers to mimic the hetero- and multivalent approach nature uses at protein-protein interfaces. The investigator will use an enzymatic strategy to sequence-specifically incorporate unique peptide fragments along a DNA template. This approach will enable the concomitant evolution of the ssDNA scaffold and the identity of the displayed peptides to achieve molecular recognition of protein targets. If successful, this new class of biomimetic polymers could aid in addressing the deficit of high-affinity reagents for biomedical research. These research efforts will be coupled with educational and training outreach at the high school, undergraduate, and graduate levels.