Issue 31, 2023

Simple purification of small-molecule-labelled peptides via palladium enolate formation from β-ketoamide tags

Abstract

Palladium enolates derived from β-ketocarbonyl compounds serve as key intermediates in various catalytic asymmetric reactions. We found that the palladium enolate formed from β-ketoamide is stable in air and moisture and we applied this property to develop a peptide purification system using β-ketoamide as a small affinity tag in aqueous media. A solid-supported palladium complex successfully captured β-ketoamide-tagged molecules as palladium enolates and released them in high yield upon acid treatment. Optimum conditions for the catch and release of tagged peptides from a mixture of untagged peptides were established. To demonstrate the value of this methodology in identifying the binding site of a ligand to its target protein, we purified and identified a peptide containing the ligand-binding site from the tryptic digest of cathepsin B labelled with a covalent cathepsin B inhibitor containing a β-ketoamide tag.

Graphical abstract: Simple purification of small-molecule-labelled peptides via palladium enolate formation from β-ketoamide tags

Supplementary files

Article information

Article type
Edge Article
Submitted
04 6 2022
Accepted
04 7 2023
First published
14 7 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, 8249-8254

Simple purification of small-molecule-labelled peptides via palladium enolate formation from β-ketoamide tags

K. Hayamizu, K. Koike, K. Dodo, M. Asanuma, H. Egami and M. Sodeoka, Chem. Sci., 2023, 14, 8249 DOI: 10.1039/D2SC03112D

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