Purification Of Synthetic Peptides
High-pressure liquid chromatography employing the multicolumn countercurrent solvent gradient purification (MCSGP) process principle has been developed as a novel purification technology for peptides produced by chemical synthesis. MCSGP offers a step change in efficiency compared to batch high-performance liquid chromatography (HPLC) processing. With MCSGP, two identical reverse-phase (RP) columns are operated in countercurrent mode, with internal recycling of impurity-containing side fractions extracting continuously pure product and discarding impurities without significant product loss. Peptides can be purified at preparative/production scale with significantly higher yield without compromising target purity. The process also allows an up to 10-fold higher productivity with typically 80% lower solvent consumption, providing an overall attractive economical production scenario and allowing pushing of the boundary of economic synthesis of long peptides. Process scenarios are modeled based on experimental data showing that for 10 kg of peptide produced per year, the upstream and downstream savings can amount to millions of US dollars.