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Stability-based approaches in chemoproteomics

Lookup NU author(s): Amy George, Dr Maria Duenas FadicORCiD, Dr Jose Luis Marin-RubioORCiD, Professor Matthias TrostORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© The Author(s), 2024. Published by Cambridge University Press. Target deconvolution can help understand how compounds exert therapeutic effects and can accelerate drug discovery by helping optimise safety and efficacy, revealing mechanisms of action, anticipate off-target effects and identifying opportunities for therapeutic expansion. Chemoproteomics, a combination of chemical biology with mass spectrometry has transformed target deconvolution. This review discusses modification-free chemoproteomic approaches that leverage the change in protein thermodynamics induced by small molecule ligand binding. Unlike modification-based methods relying on enriching specific protein targets, these approaches offer proteome-wide evaluations, driven by advancements in mass spectrometry sensitivity, increasing proteome coverage and quantitation methods. Advances in methods based on denaturation/precipitation by thermal or chemical denaturation, or by protease degradation are evaluated, emphasising the evolving landscape of chemoproteomics and its potential impact on future drug-development strategies.

Publication metadata

Author(s): George AL, Duenas ME, Marin-Rubio JL, Trost M

Publication type: Review

Publication status: Published

Journal: Expert Reviews in Molecular Medicine

Year: 2024

Volume: 26

Online publication date: 12/04/2024

Acceptance date: 22/02/2024

ISSN (electronic): 1462-3994

Publisher: Cambridge University Press


DOI: 10.1017/erm.2024.6

PubMed id: 38604802