| Autor: |
George AL; Laboratory for Biomedical Mass Spectrometry, Biosciences Institute, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK., Dueñas ME; Laboratory for Biomedical Mass Spectrometry, Biosciences Institute, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK., Marín-Rubio JL; Laboratory for Biomedical Mass Spectrometry, Biosciences Institute, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK., Trost M; Laboratory for Biomedical Mass Spectrometry, Biosciences Institute, Newcastle University, Newcastle-upon-Tyne, NE2 4HH, UK. |
| Abstrakt: |
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. |
