Biotac System For Mapping Small Molecule Interactomes

An innovative technology for understanding how small molecules interact within biological systems to enable targeted drug discovery and development.

There is a critical need for an innovative approach that overcomes the limitations of current methods requiring prior target knowledge, enables comprehensive network-scale profiling of small molecule interactions, facilitates the discovery of uncharacterized off-target effects and combinatorial polypharmacology, and systematically eliminates the unpredictability in detecting drug-induced interactome changes.

The BioTAC system represents a groundbreaking stride in the field of biotechnology, offering a novel methodology that maps the intricate interactome of small molecules within cellular environments. Utilizing bifunctional molecules, this system strategically recruits a ligandable proximity labeling enzyme to complexes bound by compounds, thereby enabling their precise identification through a process of biotinylation followed by affinity purification and mass spectrometry analysis. This innovative approach holds immense potential for drug discovery and development, especially in the realm of targeted cancer therapies, by providing a deeper understanding of small molecule mechanisms of action. As a biotechnological tool, it offers unparalleled insights into protein-ligand interactions at the molecular level, which is pivotal for therapeutic research aimed at uncovering potential side effects or mechanisms of drug resistance.

Design & Development

• Enables unbiased detection of direct targets and interactome of small molecules.
• Capable of identifying both efficacy and resistance mechanisms of drug candidates.
• Applicable to live cells and whole organisms for in situ analysis.
• Extended detection radius up to 35 nm, capturing transient and moderate affinity interactions.
• Combines precision of chemical proteomics with sensitivity of proximity labeling.

Tao, A. J., Jiang, J., Gadbois, G. E., Goyal, P., Boyle, B. T., Mumby, E. J., Myers, S. A., English, J. G., & Ferguson, F. M. (2023). A biotin targeting chimera (BioTAC) system to map small molecule interactomes in situ. Nature communications, 14(1), 8016. https://doi.org/10.1038/s41467-023-43507-5

Steven Christiansen
801.587.0915
steven.christiansen@utah.edu