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

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-ch...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2023-06, Vol.14 (25), p.6986-6991
Main Authors: Sugisawa, Naoto, Ando, Akira, Fuse, Shinichiro
Format: Article
Language:English
Subjects:
Amino acids
Chemistry
Column chromatography
Coupling
Elongation
Liquid phases
Nucleophiles
Peptides
Purification
Solid phase synthesis
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Summary: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 a one-flow, three-component coupling (3CC) approach that is the first to use α-amino acid -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 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.
ISSN:2041-6520
2041-6539
DOI:10.1039/d3sc01333b