Retrofitting HPLC hardware for affordable and accessible flow-based peptide synthesis

Abstract

Continuous-flow solid-phase peptide synthesis (SPPS) has transformed modern peptide assembly, enabling rapid synthesis and extended chain assembly (>150 amino acids) while attracting significant interest for economical, scalable and greener peptide production. However, broader adoption of flow-based SPPS is limited by its technical complexity compared to batch methods and the high cost of specialised instrumentation. Here, we establish a low-cost flow-based SPPS platform by retrofitting HPLC hardware with a custom reaction chamber compatible with commercial fritted syringes for resin handling. We demonstrate the system’s capabilities as a practical and accessible platform for chain elongation and diverse on-resin transformations, including sulfation, deallylation and macrocyclisation.

Keywords: conotoxins, continuous-flow SPPS, cyclic peptides, deallylation, flow-based peptide synthesis, macrocyclisation, solid-phase peptide-synthesis, sulfation.

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