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 Mrz 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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements