Compartmentalization of enhanced biomolecular interactions for high-throughput drug screening in test tubes
By
Min Zhou,
Weiping Li,
Jian Li,
Leiming Xie,
Rongbo Wu,
Liang Wang,
Shuai Fu,
Wei Su,
Jianyang Hu,
Jing Wang,
Pilong Li
Posted 20 Jan 2020
bioRxiv DOI: 10.1101/2020.01.19.911149
Modification-dependent and -independent biomolecular interactions (BIs), including protein-protein, protein-DNA/RNA and protein-lipid, play crucial roles in all cellular processes. Dysregulation of BIs or malfunction of the associated enzymes results in various diseases, thus they are attractive targets for therapies. High-throughput screening (HTS) can greatly facilitate the discovery of drugs for these targets. Here we describe a HTS drug discovery method, called compartmentalization of enhanced biomolecular interactions in test tubes (CEBIT). CEBIT uses selective recruitment of biomolecules into phase separated compartments harboring their cognate binding partners as readouts. CEBIT were tailored to detect various BIs and associated modifying enzymes. Using CEBIT-based HTS assays, we successfully identified known inhibitors of the p53/MDM2 interaction and of SUV39H1 from a compound library. CEBIT is simple and versatile, and is likely to become a powerful tool for drug discovery and basic biomedical research.
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