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月 2022
Accepted
04 7月 2023
First published
14 7月 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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