Issue 36, 2022

Competitive profiling of ligandable cysteines in Staphylococcus aureus with an organogold compound

Abstract

With the idea of exploiting metal templated C–S bond forming reactions to achieve modification of cysteines in bacterial proteins, a cyclometalated Au(III) compound was explored in a competitive chemoproteomic approach in S. aureus cell extracts. More than 100 ligandable cysteines were identified, of which more than 50% were not engaged by organic α-chloroacetamides in a previous study, indicating that organometallic compounds expand the ligandable space in bacteria. A selected interaction was validated using an enzyme activity assay, and intact protein mass spectrometry showed cysteine arylation of an unprecedented target. The obtained results demonstrate that this family of organogold compounds has potential for therapeutic protein targeting via selective, covalent modification of cysteine residues in bacteria.

Graphical abstract: Competitive profiling of ligandable cysteines in Staphylococcus aureus with an organogold compound

Supplementary files

Article information

Article type
Communication
Submitted
01 mar 2022
Accepted
07 apr 2022
First published
07 apr 2022

Chem. Commun., 2022,58, 5526-5529

Competitive profiling of ligandable cysteines in Staphylococcus aureus with an organogold compound

C. Schmidt, M. Zollo, R. Bonsignore, A. Casini and S. M. Hacker, Chem. Commun., 2022, 58, 5526 DOI: 10.1039/D2CC01259F

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