A Versatile Polymer Platform for Biomedical Applications

项目摘要/摘要 合成聚合物和生物系统的合并有着重要的历史，但许多 为目标应用选择的材料是根据它们的商业可用性而选择的 或访问的便利性。这些材料很少引出所有需要的特征，例如 如可降解性、生物兼容性以及对聚合物结构和组成的控制。这 计划采取了一种自下而上的方法来开发高度通用的聚合物平台 由化学创新驱动，以结合所需的设计特征和灵活性 与生物学对接。这是从Ru的强健化学开始实现的- 基于烯烃的化合作用，并将其与底物导向的化学反应的力量相结合。 有了这一总体策略，令人难以置信的强大的结扎反应被设计成迅速 将活性聚合物直接连接到其他大分子上，从而消除了 通过传统的点击化学。这将导致高度简化的生物结合策略， 同时也提供了有效去除Ru的机会。这一概念还使 设计全新的单体系列，使聚合物具有响应性 可编程瞄准、降级和货物释放的主干。通过更改 结构，降解动力学的微调可以优化，也可以重新设计以保持 生物兼容性。最后，这一战略将解决一个长期存在的挑战，即理解 合成聚合物与生命系统的相互作用：建筑。趋同战略将是 开发用来控制合成聚合物中支化的位置和程度 系统。这将导致对聚合物中结构-性质关系的剖析 目前无法使用现代技术访问的拓扑。所有这些方法结合在一起 将导致聚合物设计的真正的“药物化学”方法，在这种方法中，结构可以 根据特定的最终目标进行构建、设计和优化。

Project Summary/Abstract The merger of synthetic polymers and biological systems has a significant history, but many of the materials chosen for targeted applications are selected due to their commercial availability or ease of access. These materials rarely elicit all of the features that would be desirable such as degradability, biocompatibility, and control over polymer architecture and composition. This program takes a ground-up approach to developing a highly versatile polymer platform that is driven by chemical innovation in order to incorporate the design features and flexibility needed for interfacing with biology. This is achieved by starting with the robust chemistry of ruthenium- based olefin metathesis and merging it with the power of substrate-directed chemical reactions. With this general strategy, incredibly robust ligation reactions have been designed to rapidly conjugate living polymers directly to other macromolecules, thereby removing the need to go through traditional click chemistry. This will lead to highly simplifying bioconjugation strategies, while also presenting opportunities for efficient ruthenium removal. This concept also enables the design of entirely new monomer families that give polymers with responsive chemistry in the backbone for programmable targeting, degradation, and cargo release. By changing the structure, fine tuning of degradation kinetics can be optimized and also redesigned to maintain biocompatibility. Lastly, this strategy will tackle a longstanding challenge in understanding the interaction of synthetic polymers with living system: architecture. A convergent strategy will be developed to give control of both the location and degree of branching in synthetic polymer systems. This will lead to the dissection of structure-property relationships in the polymer topology that is currently inaccessible with modern techniques. All of these methods combined will lead to a truly “medicinal chemistry” approach to polymer design where structures can be built, designed, and optimized with the specific end goals in mind.