A Membrane Based Platform for the Synthesis of Defined Sequence Polymers

用于合成特定序列聚合物的基于膜的平台

• 批准号: 2162361
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2162361
• 关键词: Membrane; Based; Platform; Synthesis; Defined

Natural processes are able to produce polymers of exact sequence and length, such as DNA and peptides, however to date no one has been able to create synthetic polymers of a predefined sequence at a level of accuracy and efficiency close to these natural polymers. All current research focuses upon solid phase iterative synthesis, adding one monomer at a time upon a solid support. This yields significant loss of useful monomers, a rate of production that is highly diffusion limited, and prohibitive production cost. My PhD research, completed under the tutelage of Professor Andrew Livingston, will tackle these issues by combining the iterative synthesis approach with membranes recently developed, by the research group, for organic solvent nanofiltration. This will allow for the creation of sequence specific exact length synthetic polymers (or exactymers) in liquid phase reactions, rather than the solid phase described above. This will result in a new production platform for exactymer synthesis, promoting higher yields, higher purity and easier scale up then the current convention.The definite nature of this production method, coupled with the ability to functionalise each monomer uniquely, enables exactymers to have precise chemical groups at known locations. The resulting molecules can then be used for a multitude of applications depending on the functionalisation used for each individual monomer. Many of these applications only become accessible due to the high quality and quantity of the new production platform, for example in healthcare, the functionalisation can produce a molecule containing a specific combination of active pharmaceutical ingredient, imaging agent and binding ligand to create a highly targeted drug. This has the potential to revolutionise the pharmaceutical industry, reducing side effects and saving countless lives. In nanotechnology, the exactymers can be functionalised with conformation directing side chains to ensure a specific 3D shape of complex macromolecular structures. Further potential applications include information storage, where the sequence of functionalised side chains can be used for high security data storage with each side chain corresponding to a predefined figure or data packet, mimicking the function of DNA in the human body and changing the landscape of data encryption.

自然过程能够产生精确序列和长度的聚合物，如DNA和多肽，然而，到目前为止，还没有人能够以接近这些天然聚合物的精度和效率来制造预定序列的合成聚合物。目前所有的研究都集中在固相迭代合成上，在固体载体上一次添加一个单体。这会导致有用单体的大量损失，生产速度受到高度扩散的限制，以及高昂的生产成本。我的博士研究在安德鲁·利文斯顿教授的指导下完成，将通过将迭代合成方法与研究小组最近开发的用于有机溶剂纳滤的膜相结合来解决这些问题。这将允许在液相反应中产生特定序列的精确长度的合成聚合物(或精确聚合物)，而不是上述的固相。这将产生一种用于精密聚合物合成的新生产平台，促进比目前的常规更高的产率、更高的纯度和更容易的放大。这种生产方法的明确性质，加上对每个单体进行独特官能化的能力，使精密聚合物能够在已知位置具有精确的化学基团。然后，根据每个单体所使用的官能化程度，所得到的分子可用于多种应用。这些应用中的许多只有由于新生产平台的高质量和高数量才能获得，例如在医疗保健领域，官能化可以生产包含活性药物成分、显像剂和结合配体的特定组合的分子，以创建高度靶向的药物。这有可能给制药业带来革命性的变化，减少副作用，拯救无数生命。在纳米技术中，精确聚合物可以通过构象导向侧链进行功能化，以确保复杂大分子结构的特定3D形状。进一步的潜在应用包括信息存储，其中官能化侧链序列可用于高度安全的数据存储，每个侧链对应于预定义的图形或数据分组，模仿人体中DNA的功能并改变数据加密的格局。