Purification of Synthetic Peptides Using a Catching by Polymerization Approach

在这个由化学学部化学合成项目资助的项目中，密歇根理工大学化学系的方世岳教授将探索一种廉价且易于扩展的方法来纯化合成肽。多肽不仅在生物学研究中有着广泛的应用，在药物开发中也发挥着越来越重要的作用。因此，需要大量的多肽。合成多肽最方便的方法是使用合成器在固体载体上逐步组装氨基酸单体。然而，在每个单体添加步骤中，不可避免地会产生截断的失效序列。这些失效序列与全长序列具有相似的物理性质，因此难以去除。目前应用最广泛的多肽纯化方法是反相高效液相色谱法。该方法劳动强度大，消耗大量有机溶剂。在这个项目中，将开发两种廉价且易于扩展的肽纯化方法。在这两种方法中，所需的全长肽将用可聚合基团修饰。失败序列则不会。合成后，全长肽将共聚成不溶性聚合物。故障序列将通过洗涤去除。然后从聚合物中分离出纯肽。这些纯化技术一经开发，可广泛用于多肽药物的纯化。许多肽类药物的价格，包括已经上市和未来开发的肽类药物，都可以大幅降低。该项目是跨学科的，需要有机合成、固相合成、肽化学和聚合物科学方面的技能，并为各级学生提供多样化的培训平台。本科生将从芬兰大学招收，芬兰大学没有一个活跃的研究项目。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Shiyue Fang of the Department of Chemistry at Michigan Technological University will explore the development of inexpensive and readily scalable methods for the purification of synthetic peptides. Besides wide applications in biological research, peptides are becoming more and more important in drug development. As a result, large quantities of peptides are needed. The most convenient method for peptide synthesis is to assemble amino acid monomers stepwise on a solid support using a synthesizer. In each monomer addition step, however, generation of truncated failure sequences is unavoidable. These failure sequences have similar physical properties as the full-length sequence and are therefore difficult to remove. The most widely used peptide purification method is reverse-phase HPLC. This method is labor intensive and consumes large volumes of organic solvents. In this project, two inexpensive and readily scalable peptide purification methods will be developed. In both methods, the desired full-length peptide will be modified with a polymerizable group. The failure sequences will not. After synthesis, the full-length peptide will be copolymerized into an insoluble polymer. The failure sequences will be removed by washing. Pure peptide will then be cleaved from the polymer.Once developed, these purification technologies could be widely used for peptide drug purification. The price of many peptide drugs including those already on the market and the ones to be developed in the future could be lowered substantially. The project is interdisciplinary, requiring skills in organic synthesis, solid phase synthesis, peptide chemistry, and polymer science and provides a diverse training platform for students at all levels. Undergraduate students will be recruited from Finlandia University, which does not have an active research program.