Chemical Functionalization and Polymerization of Peptide Particle Assemblies

肽颗粒组装体的化学功能化和聚合

• 批准号: 2003897
• 负责人: Christopher Kloxin
• 金额: $ 44.68万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2003897&HistoricalAwards=false
• 关键词: Chemical; Functionalization; Polymerization; Peptide; Particle

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.

有了这个奖项，化学系的大分子，超分子和纳米化学项目资助特拉华州大学的Christopher Kloxin和Darrin J. Pochan教授设计和合成合成聚合物，复制并最终补充天然存在的双大分子的一些能力。 生物大分子具有精确的序列，在自然界中是通用的，并且具有执行从分子识别到催化的许多功能的折叠结构。 在这些复杂的结构中，有常见的重复出现的结构单元，如α螺旋、β折叠、卷曲螺旋和环，整个蛋白质结构都是在这些单元上构建的。 虽然自然界使用折叠的子结构作为主要的设计元素，但大多数合成聚合物缺乏这种模块化设计，功能也不那么复杂。 为了弥合这一差距，这项研究设计和制备复杂的聚合物，使用短肽序列组装成强大的和明确定义的卷曲螺旋单位称为双链体。 这些序列使用基于微波的方法快速产生，然后并入长聚合物链中。 计算建模用于设计整流器。 组装聚合物的结构特征，如稳定性和物理性能，也进行了系统的研究。 研究活动为本科生和研究生提供聚合物和材料化学方面的宝贵教育经验。 该研究团队正在进一步扩大他们的工作的影响，通过促进各种外联活动和涉及K-12学生和更广泛的社区计划。 此外，开发了类似于蛋白质银行的功能卷曲螺旋数据库，为研究人员和教育工作者提供新的资源。 该研究小组正在开发一种新的方法，用于设计和制备复杂的聚合物纳米结构，使用短肽序列组装成坚固且定义良好的螺旋-螺旋单元，称为螺旋体。 该研究利用生物组件的计算设计概念，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合物的功能化和聚合，而第二个目标是使用原子转移自由基聚合（ATRP）合成聚合物瓶、刷子和星形。 第三个目的是通过利用氨基酸与不同肽链的交联稳定组装的聚合物结构来引入双链钉合。 通过这些目标，可以建立用于组装点击官能化卷曲螺旋肽的条件和约束，以作为聚合物设计和合成的基本单元。 此外，非生物残基和共价键对卷曲螺旋的形成和稳定性以及对反应基团的可及性，定位和限制的影响进行了研究。 最后，创建具有高效点击官能团的精确外部显示的稳定的超分子组装体，通过物理（非共价）相互作用和随后通过共价相互作用的稳定化提供新的大分子组装途径的途径。 这种新的高分子制造方法有可能影响广泛的研究领域和应用，从肽基治疗到催化。该奖项反映了NSF的法定使命，并被认为值得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来支持。