Implication of Side Reactions in Iterative Biopolymer Synthesis: The Case of Membrane Enhanced Peptide Synthesis

Membrane enhanced peptide synthesis (MEPS) improves conventional liquid phase synthesis by purifying intermediate products via filtration. A challenging aspect of MEPS is the propagation of unreacted materials and byproducts throughout the iterative synthesis. In this study, we first develop and validate a model of MEPS. The model is then applied to investigate the implications of side reactions (i.e., formation of error sequences) due to incomplete reaction and insufficient removal of amino acids after coupling. Sensitivity analysis shows that increasing the reaction extent for all couplings from 90 to 100% reduces the yield of truncated sequences from 29 to 0%. The formation of repeating sequences is found to be negligible in all case studies due to the large diavolume of post-deprotection diafiltration. This study provides useful insights into the operation of MEPS with particular emphasis on the control of error sequence formation. These insights are transferable to other sequence-controlled biopolyme...

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