Automated flow peptide synthesis

Abstract

Though reported by Merrifield nearly sixty years ago, batch solid phase peptide synthesis remains slow at minutes to hours per residue. Here we report a fully automated, flow based approach to solid phase polypeptide synthesis with amide bond formation in seven seconds and total synthesis times of forty seconds per amino acid residue. Crude peptide purities and isolated yields were comparable to standard batch solid phase peptide synthesis. Process monitoring with absorbance spectroscopy allows for the immediate detection and rapid optimization of difficult-to-synthesize peptides. This instrument is flexible and allows for synthesis of peptide nucleic acids, glycopeptides, removal of orthogonal amine protecting groups, and click chemistry on the solid phase. At full capacity, this approach to peptide synthesis can yield tens of thousands of individual 30-mer peptides per year.