PT  - JOURNAL ARTICLE
AU  - Min Zhou
AU  - Weiping Li
AU  - Jian Li
AU  - Leiming Xie
AU  - Rongbo Wu
AU  - Liang Wang
AU  - Shuai Fu
AU  - Wei Su
AU  - Jianyang Hu
AU  - Jing Wang
AU  - Pilong Li
TI  - Compartmentalization of enhanced biomolecular interactions for high-throughput drug screening in test tubes
AID  - 10.1101/2020.01.19.911149
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.19.911149
4099  - http://biorxiv.org/content/early/2020/01/20/2020.01.19.911149.short
4100  - http://biorxiv.org/content/early/2020/01/20/2020.01.19.911149.full
AB  - 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.