Fatty acid chain modification of loxenatide and its kinetics in a continuous flow microchannel reactor

In this study, a continuous flow microchannel reactor was designed and constructed for continuous and efficient fatty acid chain modification (FACylation) of polypeptides to achieve higher production capacity than that obtained in a batch reactor. In this microreactor, loxenatide (LOX) was site-specifically modified by N-tetradecylmaleimide (C14-MAL) to continuously synthesize the target product, N-tetradecyl-loxenatide (C14-LOX). Based on the experimental data under different conditions, a kinetic model of FACylation was established to describe the initial stage of the continuous reaction in the microreactor. Under the optimal conditions obtained by the kinetic model, the reaction time in the microreactor could be reduced to 1/3 that of the batch reactor at the same yield, and the production capacity of the microreactor was at least 3.78 times that of the batch reactor within the same time (40 h). These results would contribute to the development of microreactors in the biopharmaceutical industry.