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Rapid Discovery of Functional Small Molecule Ligands against Proteomic Targets through Library-Against-Library Screening.
- Source :
-
ACS Combinatorial Science . 6/13/2016, Vol. 18 Issue 6, p320-329. 10p. - Publication Year :
- 2016
-
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]
Details
- Language :
- English
- ISSN :
- 21568952
- Volume :
- 18
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- ACS Combinatorial Science
- Publication Type :
- Academic Journal
- Accession number :
- 116199971
- Full Text :
- https://doi.org/10.1021/acscombsci.5b00194