Continuous flow solid (gel) phase peptide synthesis using unsupported ultra-high load polymers

A simple, manually operated, continuous flow apparatus is described for solid (gel) phase peptide synthesis. The approach uses an unsupported phenolic bead form core network at an initial matrix loading of 5 mmol g-1, the theoretical maximum. The synthesis is performed in a flow reactor under low pressure conditions. "Layered displacement" of reagent solutions and washing solvents is an essential feature that has been developed to facilitate efficient peptide synthesis. The usefulness of the present system in conjunction with N alpha Boc protected amino acids is illustrated by the syntheses of [Leu5]-enkephalin and dermorphin. The potential for scale up synthesis has also been investigated.