Comparison of Microwave and Conduction Heating for Solid Phase Peptide Synthesis

Abstract

Solid phase peptide synthesis (SPPS) has become a standard approach for synthesis of peptides, especially in a laboratory setting. Heating the reactions in SPPS could significantly reduce the coupling and deprotection times. One of the heating methods is to use microwave which is becoming increasingly popular because it not only dramatically reduces the synthesis times, but also increases the crude peptide purity [1]. However, microwave peptide synthesizers are relatively expensive. In this study, we investigated whether SPPS using conduction heating can achieve similar result as microwave irradiation. CSBIO II and CEM Liberty Blue were used as heating resource of conduction and microwave heating, respectively. Four peptides with length of 18mer, 19mer, 20mer (Bivalirudin) and 39mer (Exenatide) were selected as examples. The peptides were synthesized using the same synthesis protocol at 90 ºC including identical coupling, deprotection and washing cycles. The differences between the two approaches are the temperature of washing DMF (90 ºC vs 23 ºC for conduction and microwave heating, respectively) and overall synthesis cycle time (17 min vs 13 min in conduction and microwave heating, respectively). Both conduction and microwave heating generated comparable results with crude purity of 52.0% vs 51.7%, 49.0% vs 57.3%, 62.8% vs 57.1%, 37.0% vs 30.5% for 18mer, 19mer, 20mer and 39mer, respectively. One of the advantages of conduction heating is the uniformly and consistently delivered temperature during the synthesis which could minimize racemization and side reactions caused by spikes and hotspots typically associated with microwave heating. In addition, conduction heating is also a more cost-efficient heating method when compared to expensive microwave heating technology.

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