Issue 25, 2023

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.

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

Supplementary files

Article information

Article type
Edge Article
Submitted
13 Mar 2023
Accepted
04 Jun 2023
First published
12 Jun 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 6986-6991

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

N. Sugisawa, A. Ando and S. Fuse, Chem. Sci., 2023, 14, 6986 DOI: 10.1039/D3SC01333B

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