Nanoparticle Materials as Chemical and Biological Tools for Peptides and Proteins

纳米颗粒材料作为肽和蛋白质的化学和生物工具

• 批准号: 2308625
• 负责人: Yan Zhao
• 金额: $ 50万
• 依托单位: Iowa State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2308625&HistoricalAwards=false
• 关键词: Nanoparticle; Materials; Chemical; Biological; Tools

NON-TECHNICAL SUMMARYProteins are workhorses of cells and involved in practically every single biological process. Selective labeling of proteins is important to the elucidation of their mechanisms, understanding of their functions, and improvement in the properties of therapeutic proteins such as prolonged circulation time, reduced immunogenicity, and/or better proteolytic stability. The research group of Professor Yan Zhao at Iowa State University develops antibody-mimicking polymeric nanoparticles to recognize specific parts of proteins and deliver fluorescent tags, affinity labels, or polymeric reagents precisely to the targeted sites. These site-specifically labeled proteins are useful in many applications including biological studies of protein functions, tracing proteins in their cellular fates, and purification of proteins. These nanoparticles are inexpensive, robust synthetic materials that do not denature as fragile biomolecules and can be produced in large quantities without using live animals. They have the potential to replace antibodies under many research and biotechnology settings. The multidisciplinary research helps trains student researchers into professional scientists by exposing them to a wide range of skills in biomaterials science, biology, physical organic chemistry, supramolecular chemistry, and polymer chemistry.TECHNICAL SUMMARYProteins rarely work alone in their biological functions but are regulated through post-translational modifications (PTMs), protein–protein interactions (PPIs), and other mechanisms. Mapping out these PTMs and PPIs is key to fundamental biology and drug development, and frequently requires selective modification of proteins, as well as selective protein-binding materials. The latter is also useful for a range of other purposes including protein purification, detection, and replacement of antibodies in certain applications. This project, funded by the Biomaterials Program of the Materials Research Division, supports Professor Yan Zhao of Iowa State University to develop antibody-mimicking polymeric nanoparticles that to bind proteins with high affinity and specificity. Aim 1 focuses on the site-specific labeling of protein with a single or multiple tags. Aim 2 focuses on the development nanoparticle receptors to bind surface groups of proteins. These materials are prepared through molecular imprinting within cross-linked surfactant micelles. They are expected to impact multiple research fields including fundamental biochemistry and cell biology, biotechnology, and protein therapeutics. The education and outreach activities center on participation in on- and off-campus programs to engage undergraduate research and increase STEM exposure to K–12 students. In addition, the PI uses several methods to familiarize students with patents and the patenting process and to better prepare them for industrial careers.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.

非技术性总结蛋白质是细胞的主力，几乎参与每一个生物过程。蛋白质的选择性标记对于阐明其机制、理解其功能以及改善治疗性蛋白质的性质（例如延长的循环时间、降低的免疫原性和/或更好的蛋白水解稳定性）是重要的。爱荷华州州立大学的赵岩教授的研究小组开发了抗体模拟聚合物纳米颗粒，以识别蛋白质的特定部分，并将荧光标签，亲和标签或聚合物试剂精确地传递到目标部位。这些位点特异性标记的蛋白质在许多应用中是有用的，包括蛋白质功能的生物学研究、在蛋白质的细胞命运中追踪蛋白质以及蛋白质的纯化。这些纳米颗粒是廉价的，坚固的合成材料，不会变性为脆弱的生物分子，并且可以在不使用活体动物的情况下大量生产。它们有可能在许多研究和生物技术环境中取代抗体。多学科的研究有助于培养学生研究人员成为专业的科学家，通过暴露他们在生物材料科学，生物学，物理有机化学，超分子化学和聚合物化学的广泛技能。技术总结蛋白质很少单独发挥其生物功能，但通过翻译后修饰（PTM），蛋白质-蛋白质相互作用（PPI）和其他机制进行调节。绘制这些PTM和PPI是基础生物学和药物开发的关键，并且经常需要选择性修饰蛋白质以及选择性蛋白质结合材料。后者也可用于一系列其他目的，包括蛋白质纯化、检测和某些应用中的抗体置换。该项目由材料研究部生物材料计划资助，支持爱荷华州州立大学的赵岩教授开发具有高亲和力和特异性结合蛋白质的抗体模拟聚合物纳米颗粒。目的1是利用单个或多个标签对蛋白质进行位点特异性标记。目标2专注于开发结合蛋白质表面基团的纳米颗粒受体。这些材料是通过交联表面活性剂胶束内的分子印迹制备的。预计它们将影响多个研究领域，包括基础生物化学和细胞生物学，生物技术和蛋白质治疗学。教育和外展活动的中心是参与校内和校外项目，以从事本科生研究，并增加K-12学生的STEM接触。此外，PI还使用多种方法来帮助学生熟悉专利和专利申请流程，并为他们的工业生涯做好更好的准备。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。