Rapid Discovery of Functional Small Molecule Ligands against Proteomic Targets through Library-Against-Library Screening

Chun Yi Wu, Don Hong Wang, Xiaobing Wang, Seth M. Dixon, Liping Meng, Sara Ahadi, Daniel H. Enter, Chao Yu Chen, Jason Kato, Leonardo J. Leon, Laura M. Ramirez, Yoshiko Maeda, Carolina F. Reis, Brianna Ribeiro, Brittany Weems, Hsing Jien Kung, Kit S. Lam

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6 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)320-329
頁數10
期刊ACS Combinatorial Science
18
發行號6
DOIs
出版狀態已發佈 - 六月 13 2016
對外發佈Yes

ASJC Scopus subject areas

  • Chemistry(all)

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