Issue 1, 2024

A cell-permeable probe for the labelling of a bacterial glycosyltransferase and virulence factor

Abstract

Chemical probes for bacterial glycosyltransferases are of interest for applications such as tracking of expression levels, and strain profiling and identification. Existing probes for glycosyltransferases are typically based on sugar-nucleotides, whose charged nature limits their applicability in intact cells. We report the development of an uncharged covalent probe for the bacterial galactosyltransferase LgtC, and its application for the fluorescent labelling of this enzyme in recombinant form, cell lysates, and intact cells. The probe was designed by equipping a previously reported covalent LgtC inhibitor based on a pyrazol-3-one scaffold with a 7-hydroxycoumarin fluorophore. We show that this pyrazol-3-ones scaffold is surprisingly stable in aqueous media, which may have wider implications for the use of pyrazol-3-ones as chemical probes. We also show that the 7-hydroxycoumarin fluorophore leads to an unexpected improvement in activity, which could be exploited for the development of second generation analogues. These results will provide a basis for the development of LgtC-specific probes for the detection of LgtC-expressing bacterial strains.

Graphical abstract: A cell-permeable probe for the labelling of a bacterial glycosyltransferase and virulence factor

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Article information

Article type
Paper
Submitted
15 6月 2023
Accepted
18 10月 2023
First published
19 10月 2023
This article is Open Access
Creative Commons BY license

RSC Chem. Biol., 2024,5, 55-62

A cell-permeable probe for the labelling of a bacterial glycosyltransferase and virulence factor

Y. Xu and G. K. Wagner, RSC Chem. Biol., 2024, 5, 55 DOI: 10.1039/D3CB00092C

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