Degradation by transesterification on demand: RNA-inspired degradation motifs in synthetic poly(phospho)esters

按需酯交换降解：合成聚（磷酸）酯中受 RNA 启发的降解基序

• 批准号: 267144673
• 负责人: Professor Dr. Frederik Wurm
• 金额: --
• 依托单位: Sustainable Polymer Chemistry Group
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/267144673?language=en
• 关键词: Degradation; transesterification; demand; RNA; inspired

Degradable polymers are important materials for medical applications ("drug delivery", implants, "tissue engineering") and are in great demand as alternatives to traditional plastics, e.g. in the packaging industry. Most degradable polymers are based on polyesters or their copolymers. The degradation rates are only limited variable. This project proposal uses the versatile polyphosphoesters (PPE) to realize polymers with molecularly adjustable degradation rates (from seconds to months). The hydrolysis of PPE does not occur by random cleavage of the ester functions in the main chain, but preferably follows a so-called "back-biting" mechanism of the terminal OH group with the polymer chain. This motif will be synthetically introduced into the side chain of polymers in order to achieve a molecular control of the degradation rates. This mechanism is reminiscent of RNA, which transesterifies rapidly in water due to the large number of OH groups in the ribose units and thereby degrades. The project presents the systematic synthesis of cyclic phosphate and phosphonate monomers bearing blocked OH functions, which are released after polymerization. Due to the adjustable proximity and nucleophilicity of the OH functions to the polyester backbone, the degradation rates are to be controlled. Also, a variation of phosphate and phosphonate backbone with additional OH functions allows further control of degradation rate. In addition, protected ("photocaged") polymers are to be synthesized, which allow degradation “on demand”, by very rapid transesterification after cleavage of the protective groups. These PPEs will be investigated in enzyme-polymer conjugates and hydrogels with adjustable degradation rates. The developed synthetic cleavage sites for PPE are also expected to accelerate the degradation kinetics of polylactide, the most common "biodegradable" plastic today, as it degrades much too slowly in many areas. Overall, with the proposed project, the production of degradable poly(phospho) esters with precisely adjustable degradation rates will be possible, which to the best of my knowledge cannot be achieved with any other polymer class today. The findings of these syntheses will allow the use of the developed "cleavage sites" in a variety of applications in medicine and materials science.

可降解聚合物是医疗应用（“药物输送”、植入物、“组织工程”）的重要材料，并且作为传统塑料的替代品有着巨大的需求，例如在包装行业中，大多数可降解聚合物都是基于聚酯或其共聚物降解。该项目建议使用多功能聚磷酸酯（PPE）来实现分子可调节的降解速率（从几秒到几个月）。PPE 的水解不会随机发生。主链中酯官能团的裂解，但优选遵循末端OH基团与聚合物链的所谓“反向咬合”机制。该基序将被合成地引入到聚合物的侧链中，以实现这种机制让人想起RNA，由于核糖单元中存在大量羟基，RNA 在水中快速发生酯交换，从而降解。聚合后释放的 OH 官能团由于 OH 官能团与聚酯主链的亲核性可调节，因此可以控制降解速率。此外，具有附加 OH 官能团的磷酸酯和膦酸酯主链的变化可以进一步控制。此外，将合成受保护的（“光笼”）聚合物，这些聚合物可以在保护基团裂解后通过非常快速的酯交换反应“按需”降解。所开发的 PPE 合成裂解位点也有望加速聚丙交酯（当今最常见的“可生物降解”塑料）的降解动力学，因为总体而言，聚丙交酯在许多领域的降解速度太慢。 ，通过拟议的项目，生产具有精确可调降解率的可降解聚（磷酸）酯将成为可能，据我所知，目前任何其他聚合物类别都无法实现这一目标。合成将允许在医学和材料科学的各种应用中使用开发的“切割位点”。