A Conduction Pre-Heating System to Optimize Solid Phase Peptide Synthesis

Abstract

Solid-phase peptide synthesis (SPPS) is the preferred method for peptide preparation in both research and industry. One of the key advantages of SPPS is its ability to be fully automated. Accordingly, various types of peptide synthesizers are available on the market. The efficiency of peptide synthesis depends on several factors, including the choice of resin, protecting groups, coupling reagents, and solvents, as well as the capabilities of the peptide synthesizer. Another crucial parameter is temperature, which significantly affects the yield, purity of the target peptide, and overall synthesis time. Conduction heating has been shown to provide uniform and controlled heating for precise temperature control. However, reaction temperature equilibration can be a bottleneck due to the time required for reagents to reach the target temperature within the reaction vessel. Pre-heating reagents and solvents prior to transfer to the heated reaction vessel can help reduce the time to reach the equilibration temperature and possibly improve yield and peptide crude purity using shorter reaction times. To this purpose, we incorporated a heat exchanger on the CSBio 136X to pre-heat reagents and solvents prior to delivery to the thermostated reaction vessel. We examined permutations of different reaction temperatures varying coupling and deprotection times on a 0.1 mmol synthesis of several model peptides. The heat exchanger allowed us to reduce the time /cycle while tightly controlling the temperature of the reaction. This methodology is envisaged to be easily scalable to larger batch synthesis.

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