Abstract
The polymer monolith for solid-phase synthesis was prepared through in situ copolymerization of chloromethylstyrene and ethylene glycol dimethacrylate (PCMS-EDMA), and the obtained monolith was grafted by poly (ethylene glycol) acrylate monomer via activators generated by electron transfer atom transfer radical polymerization (AGET ATRP). The novel monolith was highly crosslinked and showed no detectable swelling in both polar and nonpolar solvents (e.g. dichloromethane, dimethylformamide, tetrahydrofuran, acetonitrile, and methanol). The grafted monolith increased the number of functional groups in the range of 0.32–0.85 mmol/g, which resulted from side groups in each grafting polymer chain. Meanwhile, the grafted monolith showed good permeability and mechanical strength under the flow-through conditions. This monolith was derived into Wang resin and used in the synthesis of a difficult sequence-acyl carrier protein fragment 65–74 (ACP 65–74) in a new designed continuous flow equipment. The yield and purity of the crude peptide acquired from the grafted monolith reached 82% and 92%, respectively, which were higher than those by the ungrafted monolith (51% and 60%, respectively) or commercial Wang resin (51% and 61%, respectively). The synthetic efficiency on the grafted monolith in the continuous flow technique was 4–5 folds higher than on Wang resins in the manually operation conditions. Therefore, this monolithic resin showed potential effects in production scale-up.
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