Chemoproteomics, A Broad Avenue to Target Deconvolution

As a vital project of forward chemical genetic research, target deconvolution aims to identify the molecular targets of an active hit compound. Chemoproteomics, either with chemical probe-facilitated target enrichment or probe-free, provides a straightforward and effective approach to profile the target landscape and unravel the mechanisms of action. Canonical methods rely on chemical probes to enable target engagement, enrichment, and identification, whereas click chemistry and photoaffinity labeling techniques improve the efficiency, sensitivity, and spatial accuracy of target recognition. In comparison, recently developed probe-free methods detect protein-ligand interactions without the need to modify the ligand molecule. This review provides a comprehensive overview of different approaches and recent advancements for target identification and highlights the significance of chemoproteomics in investigating biological processes and advancing drug discovery processes. Striving to identify the molecular targets of a bioactive compound, target deconvolution acts as the link between phenotypic chemical screening and comprehensive exploration of the underlying mechanisms. Various chemoproteomic approaches, facilitated by chemical probe-assisted target enrichment or probe-free methodologies, have been developed and employed in target deconvolution. These approaches significantly contribute to elucidating biological mechanisms and advancing drug discovery processes.image

Automated summary

Target deconvolution is a vital project in forward chemical genetic research, aiming to identify the molecular targets of active hit compounds. Chemoproteomics, employing either chemical probe-assisted target enrichment or probe-free methodologies, provides a straightforward and effective approach to profile the target landscape and unravel the mechanisms of action.