Nanoparticle Materials as Chemical and Biological Tools for Peptides and Proteins

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、了解其功能以及改善治疗性蛋白质的特性（如延长循环时间、降低免疫原性和/或更好的蛋白水解稳定性）非常重要。爱荷华州立大学赵岩教授的研究小组开发了模拟抗体的聚合纳米颗粒，以识别蛋白质的特定部分，并将荧光标签、亲和标签或聚合试剂精确地传递到目标位置。这些位点特异性标记的蛋白质在许多应用中都很有用，包括蛋白质功能的生物学研究，追踪蛋白质的细胞命运，以及蛋白质的纯化。这些纳米颗粒是廉价、坚固的合成材料，不会变性为脆弱的生物分子，可以在不使用活体动物的情况下大量生产。在许多研究和生物技术环境下，它们有可能取代抗体。多学科的研究有助于培养学生研究人员成为专业科学家，使他们接触到生物材料科学，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。技术概述：蛋白质很少单独发挥其生物学功能，而是通过翻译后修饰（PTMs）、蛋白-蛋白相互作用（PPIs）和其他机制进行调节。绘制这些ptm和PPIs是基础生物学和药物开发的关键，通常需要对蛋白质进行选择性修饰，以及选择性蛋白质结合材料。后者也可用于一系列其他用途，包括蛋白质纯化，检测和在某些应用中替代抗体。该项目由材料研究部生物材料项目资助，支持爱荷华州立大学赵岩教授开发模拟抗体的聚合纳米颗粒，以高亲和力和特异性结合蛋白质。目的1侧重于用单个或多个标签对蛋白质进行位点特异性标记。目标2的重点是开发纳米颗粒受体来结合蛋白质的表面基团。这些材料是通过分子印迹在交联表面活性剂胶束内制备的。它们有望影响多个研究领域，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。教育和推广活动的中心是参与校园内外的项目，以参与本科生的研究，并增加K-12学生接触STEM的机会。此外，PI使用几种方法让学生熟悉专利和专利申请过程，并为他们的工业生涯做好更好的准备。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。

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.