Chemical Functionalization and Polymerization of Peptide Particle Assemblies

有了这个奖项，化学系的大分子、超分子和纳米化学项目将资助特拉华大学的Christopher Kloxin教授和Darrin J. Pochan教授设计和合成合成聚合物，这些聚合物可以复制并最终补充自然产生的双大分子的一些能力。生物大分子具有精确的序列，在自然界中是普遍的，并且具有折叠结构，执行从分子识别到催化的许多功能。在这些复杂的结构中，有常见的重复出现的结构单元，如螺旋、薄片、线圈和环，它们是构建整个蛋白质结构的基础。虽然自然界使用折叠子结构作为主要设计元素，但大多数合成聚合物缺乏这种模块化设计，功能不太复杂。为了弥补这一差距，本研究设计并制备了复杂的聚合物，使用短肽序列组装成坚固且定义良好的线圈-线圈单元，称为束状聚合物。这些序列是使用基于微波的方法快速产生的，然后结合到长聚合物链中。采用计算模型设计捆绑器。组装聚合物的结构特征，如稳定性和物理性质，也进行了系统的研究。研究活动为本科生和研究生在聚合物和材料化学方面提供了宝贵的教育经验。研究小组通过参与各种涉及K-12学生和更广泛社区的外展活动和项目，进一步扩大了他们工作的影响。此外，一个功能卷曲线圈的数据库，类似于蛋白质库，被开发为研究人员和教育工作者提供新的资源。研究小组正在开发一种新的方法来设计和制备复杂的聚合物纳米结构，该方法使用短肽序列组装成坚固且定义良好的线圈-线圈单元，称为束状聚合物。该研究利用生物组件计算设计的概念来重新设计具有新交联和功能化能力的非生物纳米材料。该项目涉及三个不同的目标。第一个目标是了解聚束剂的功能化和聚合，第二个目标是利用原子转移自由基聚合（ATRP）合成聚束剂瓶刷和星形。第三个目标是通过利用氨基酸与不同肽链的交联来稳定组装的聚合物结构，从而引入束聚物钉接。通过这些目标，可以建立作为聚合物设计和合成基本单元的点击功能化卷曲肽的装配条件和约束。此外，研究了非生物残基和共价键对线圈形成和稳定性的影响，以及对反应基可及性、定位和约束的影响。最后，稳定的超分子组装与高效的点击官能团的精确外部显示被创建，通过物理（非共价）相互作用和随后的共价相互作用稳定提供了新的大分子组装途径。这种大分子制造的新方法有可能影响广泛的研究领域和应用，从基于肽的治疗到催化。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。

With this award, the Macromolecular, Supramolecular and Nanochemistry Program in the Division of Chemistry is funding Professors Christopher Kloxin and Darrin J. Pochan of the University of Delaware to design and synthesize synthetic polymers that replicate and ultimately complement some of the capabilities of naturally occurring bimoacromolecules. Biomacromolecules have precise sequences, are universal in nature, and have folded structures the perform numerous functions, from molecular recognition to catalysis. Within these complex structures, there are common reoccurring structural units such as alpha helices, beta sheets, coiled coils and loops upon which the overall protein structure is build. While nature uses folded substructures as a major design element, the majority of synthetic polymers lack such modular design and are less functionally sophisticated. To bridge this gap, this research designs and prepares complex polymers using short peptide sequences that assemble into robust and well defined coil-coil units called bundlemers. These sequences are rapidly produced using microwave-based methods and are then incorporated into long polymer chains. Computational modelling is used to design bundlemers. Structural features of assembled polymers, such as stability and physical properties, are also systematically investigated. Research activities provide undergraduate and graduate students with valuable educational experience in polymer and materials chemistry. The research team is further broadening the impact of their work by contributing to various outreach activities and programs that involve K-12 students and broader community. Additionally, a database of functional coiled-coils, analogous to the protein bank, is developed to provide new resources to researchers and educators. The research team is developing a new approach for designing and preparing complex polymeric nanostructures using short peptide sequences that assemble into robust and well defined coil-coil units called bundlemers. The research leverages concepts from computational design of biological assemblies for the de novo design of nonbiological nanomaterials with new crosslinking and functionalization capabilities. The project involves three distinct objectives. The first objective is to understand bundlemer functionalization and polymerization while the second is to synthesize bundlemer bottles brushes and stars using atom transfer radical polymerization (ATRP). The third objective is to introduce bundlemer stapling by stabilizing assembled polymeric structures utilizing crosslinking of amino acids with different peptide chains. Through these objectives, the conditions and constraints for the assembly of click-functionalized coiled-coil peptides to be implemented as a fundamental unit for polymer design and synthesis may be established. Additionally, the effect of non-biological residues and covalent linkages on coiled-coil formation and stability as well as on reactive group accessibility, localization, and confinement is investigated. Finally, stable supramolecular assembles with precise exterior displays of highly efficient click functional groups are created, providing routes to new macromolecular assembly pathways though physical (noncovalent) interactions and subsequent stabilization via covalent interactions. This new methodology for macromolecule fabrication has the potential to impact a wide range of research areas and applications, ranging from peptide-based therapeutics to catalysis.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.