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A Biotin Targeting Chimera (BioTAC) System to Map Small Molecule Interactomes in situ
Andrew J Tao1, Jiewei Jiang1, Gillian E Gadbois1
1Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093.
Biorxiv : the Preprint Server for Biology
|September 4, 2023
Summary
This study introduces BioTAC, a novel proximity labeling platform for unbiased identification of proteins interacting with small molecules. BioTAC efficiently detects direct and complexed binding proteins, including those involved in molecular glue mechanisms.
Area of Science:
- Chemical biology
- Proteomics
- Drug discovery
Background:
- Target-focused approaches for small molecule interactome profiling have limitations.
- Unbiased methods are needed to identify novel targets and understand complex interactions.
- Current proximity labeling techniques may not fully capture all small molecule-protein interactions.
Approach:
- Developed the BioTAC (small-molecule guided proximity labelling) system.
- BioTAC enables direct readout of protein interactome remodeling induced by small molecules.
- The platform incorporates chemical off-compete controls for high-confidence target identification.
Key Points:
- BioTAC rapidly identifies both direct and complexed small molecule binding proteins.
- The system overcomes limitations of existing proximity labeling platforms.
- Successfully supports identification of both inhibitor-bound and molecular glue-bound complexes.
Conclusions:
- BioTAC offers an unbiased chemical biology strategy for comprehensive interactome analysis.
- This platform advances the understanding of small molecule mechanisms of action.
- Enables discovery of novel drug targets and therapeutic strategies.
