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.