Stability-based approaches in chemoproteomics

Amy L. George, Maria Emilia Dueñas, José Luis Marín-Rubio, Matthias Trost

Research output: Contribution to journalReview articlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere6
JournalExpert Reviews in Molecular Medicine
Volume26
DOIs
Publication statusPublished - 12 Apr 2024
Externally publishedYes

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