GAP Peptide Synthesis (GAP-PS) is remarkably cost effective, combining the advantages of both solution phase and F-moc chemistry. Coupling reactions are run in solution, near the saturation point of the solvent of choice. The approach creates significant economic advantages due to reduction in both solvent and other raw material waste. The reduction in material consumption translates to significant savings in addition to the process being environmentally sensitive – enabling reuse and recycling in some cases.
Using published data from a prominent peptide CMO, we completed a detailed, comparative assessment between GAP-PS and SPPS. Choosing an example 5-mer peptide as the basis for comparison, we analyzed costs per coupling step across methods. Key savings estimates identified in that 2019 comparison included >80% reduction in anchor cost achieved by replacing the SPPS resin with the GAP protecting group. Currently, compared to SPPS, estimates show GAP-PS reduces solvent costs by >60%. In total, it is estimated today that GAP-PS can reduce raw material costs by more than 50% and is estimated to reduce labor cost by 30-45%. These estimates are, of course, intended to provide a benchmark and can vary depending on the specific target.
Because GAP-PS coupling reactions are highly efficient, deletion / insertion impurities are rare. This translates to higher crude peptide purity, which can further reduce production costs during chromatographic purification. In some cases, such as for cosmetic products, the crude purity is sufficient, and chromatography is not needed.