A Membrane Based Platform for the Synthesis of Defined Sequence Polymers

天然过程能够产生精确序列和长度的聚合物，例如DNA和肽，然而迄今为止，还没有人能够以接近这些天然聚合物的准确性和效率水平产生预定义序列的合成聚合物。目前所有的研究都集中在固相迭代合成上，在固体载体上一次加入一种单体。这导致有用单体的显著损失、高度扩散受限的生产速率和过高的生产成本。我的博士研究在Andrew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有机溶剂纳滤膜相结合来解决这些问题。这将允许在液相反应而不是上述固相中产生序列特异性精确长度的合成聚合物（或精确聚合物）。这将为exactymer合成提供一个新的生产平台，与目前的常规方法相比，可以提高产率、纯度，并更容易扩大规模。这种生产方法的明确性质，加上能够独特地官能化每个单体，使exactymer能够在已知位置具有精确的化学基团。然后，所得分子可以用于多种应用，这取决于用于每个单体的官能化。由于新生产平台的高质量和数量，这些应用中的许多应用才变得可访问，例如在医疗保健中，功能化可以产生含有活性药物成分，成像剂和结合配体的特定组合的分子，以产生高度靶向的药物。这有可能彻底改变制药行业，减少副作用并挽救无数生命。在纳米技术中，精确聚合物可以用构象导向侧链官能化，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，其中功能化侧链的序列可用于高安全性数据存储，其中每个侧链对应于预定义的图形或数据包，模仿人体中DNA的功能并改变数据加密的前景。

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.