A brief introduction to chemical proteomics for target deconvolution.

Area of Science:

• Chemical proteomics
• Drug discovery
• Pharmacology

Background:

• Drug-target relationships are fundamental to polypharmacology and drug discovery.
• Target deconvolution is essential but challenging due to proteomic complexity and limited compound affinity.
• Identifying all drug targets is a significant hurdle in phenotypic screening.

Purpose of the Study:

• To provide a comprehensive overview of chemical proteomics methods for target deconvolution.
• To categorize existing target discovery techniques.
• To discuss recent advancements in Mass Spectrometry for target identification.

Main Methods:

• Literature search of Web of Science and PubMed (1953-2022) using keywords: Drug targets, Target deconvolution, Chemical Proteomics.
• Inclusion of approximately 120 representative articles after excluding duplicates and reviews.
• Categorization of methods into biochemical enrichment and proteomics-screening approaches.

Main Results:

• Target discovery methods are broadly classified into biochemical enrichment and proteomics-screening.
• Biochemical enrichment offers ease of use and broad coverage but requires high affinity and struggles with direct/indirect target differentiation.
• Proteomics-screening methods do not need drug modification but have limited coverage and similar differentiation issues.

Conclusions:

• Current target discovery methods have inherent advantages and disadvantages.
• There is a need for novel strategies to enhance proteome coverage and target specificity.
• Further advancements are required to overcome limitations in identifying all drug targets.