Stability-based approaches in chemoproteomics.
Expert Rev Mol Med
; 26: e6, 2024 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-38604802
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteoma
/
Descoberta de Drogas
Limite:
Humans
Idioma:
En
Revista:
Expert Rev Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido