1. Rapid Discovery of Functional Small Molecule Ligands against Proteomic Targets through Library-Against-Library Screening.
- Author
-
Chun-Yi Wu, Don-Hong Wang, Xiaobing Wang, Dixon, Seth M., Liping Meng, Ahadi, Sara, Enter, Daniel H., Chao-Yu Chen, Jason Kato, Leon, Leonardo J., Ramirez, Laura M., Yoshiko Maeda, Reis, Carolina F., Ribeiro, Brianna, Weems, Brittany, Hsing-Jien Kung, and Lam, Kit S.
- Abstract
Identifying "druggable" targets and their corresponding therapeutic agents are two fundamental challenges in drug discovery research. The one-bead-one-compound (OBOC) combinatorial library method has been developed to discover peptides or small molecules that bind to a specific target protein or elicit a specific cellular response. The phage display cDNA expression proteome library method has been employed to identify target proteins that interact with specific compounds. Here, we combined these two high-throughput approaches, efficiently interrogated approximately 1013 possible molecular interactions, and identified 91 small molecule compound beads that interacted strongly with the phage library. Of 19 compounds resynthesized, 4 were cytotoxic against cancer cells; one of these compounds was found to interact with EIF5B and inhibit protein translation. As more binding pairs are confirmed and evaluated, the "library-against-library" screening approach and the resulting small molecule""protein domain interaction database may serve as a valuable tool for basic research and drug development. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF