Flow Peptide Synthesis in a Microchannel with a Reciprocating Flow of Resin Slurry

Abstract

Peptides are molecules of paramount importance in several elds, especially pharmaceuticals, healthcare, and nutrition. They are mainly obtained from solid-phase peptide synthesis (SPPS). SPPS is a cyclic process with four steps in each cycle: deprotection, washing, coupling, and rewashing. As a result, SPPS typically has a long coupling time, large excesses of reagents, and many repetitive washing steps between each step. We report the development of ow peptide synthesis in a microchannel. A ow peptide synthesizer consisted of a 1-mm-wide and 0.2-mm-deep microchannel on a glass plate and a stop-cock for a resin trap. During the coupling reaction, two syringes made a reciprocating ow of resin slurry in the microchannel to restrain aggregation and blockage of resin beads. Model peptides (Met-enkephalin) were synthesized in a continuous-ow manner. The coupling time of 10 min produced improved yields and fewer side products than that of 40 min with a conventional batch synthesis. Additionally, two equivalents of amino acid gave a desirable yield similar to that of four equivalents of amino acid in the microchannel. Therefore, the ow peptide synthesis in a microchannel can contribute to signi cantly reducing the total coupling time and consumption of amino acid.