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 |
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頁(從 - 到) | 320-329 |
頁數 | 10 |
期刊 | ACS Combinatorial Science |
卷 | 18 |
發行號 | 6 |
DOIs | |
出版狀態 | 已發佈 - 6月 13 2016 |
對外發佈 | 是 |
ASJC Scopus subject areas
- 一般化學