Rapid and column-chromatography-free peptide chain elongation via a one-flow, three-component coupling approach.

ABSTRACT: Short peptides are extremely important as drugs and building blocks for the syntheses of longer peptides. Both solid- and liquid-phase peptide syntheses suffer from a large number of synthetic steps, high cost, and/or tedious purification. Here, we developed a rapid, mild, inexpensive, and column-chromatography-free peptide chain elongation via a one-flow, three-component coupling (3CC) approach that is the first to use α-amino acid N-carboxy anhydrides (α-NCAs) both as electrophiles and nucleophiles. We demonstrated the high-yielding and column-chromatography-free syntheses of 17 tripeptides, as well as a gram-scale synthesis of a tripeptide. The total synthesis of beefy meaty peptide was achieved by repeating the 3CC approach with the addition of only one column chromatographic purification. We also demonstrated a one-flow tripeptide synthesis via in situ preparation of α-NCA starting from three readily available protected amino acids. With this study, we achieved dramatic reductions in both time and cost compared with typical solid-phase synthesis.

SUBMITTER: Sugisawa N 

PROVIDER: S-EPMC10306071 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature