Faster And Cleaner Peptide Synthesis

Solid-phase peptide synthesis is an indispensable method for constructing natural and modified peptide sequences. But the multistep process needed is time-consuming and generates a significant amount of chemical waste relative to the small amount of peptide generated. For example, a 100-mg synthesis of a peptide 20 amino acids long can take 24 hours to complete and produce several liters of waste. Jonathan M. Collins and coworkers at CEM Corp., a manufacturer of microwave reactors, have developed a high-efficiency solid-phase peptide synthesis method that cuts cycle time to four minutes and produces high-purity peptides while using 90% less solvent than conventional approaches (Org. Lett. 2014, DOI: 10.1021/ol4036825). Solid-phase peptide synthesis involves attaching a protected amino acid to a polymer bead and then coupling additional amino acids one at a time to build the peptide chain. This stepwise cycle requires deprotection, coupling, and reprotection steps at the terminal end of the growing chain. Among the improvements, the researchers found that precisely controlled rapid microwave heating helps prevent peptide aggregation and that solvent selection and streamlined washing steps lead to faster cycle times. The CEM team used the method to prepare acyl carrier protein and amyloid-β peptide with up to 93% purity in less than four hours.