國家衛生研究院 NHRI:Item 3990099045/9720
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    题名: Rapid discovery of functional small molecule ligands against proteomic targets through library-against-library screening
    作者: Wu, CY;Wang, DH;Wang, X;Dixon, SM;Meng, L;Ahadi, S;Enter, DH;Chen, CY;Kato, J;Leon, LJ;Ramirez, LM;Maeda, Y;Reis, CF;Ribeiro, B;Weems, B;Kung, HJ;Lam, KS
    贡献者: Institute of Molecular and Genomic Medicine
    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.
    日期: 2016-06
    關聯: ACS Combinatorial Science. 2016 Jun;18(6):320-329.
    Link to: http://dx.doi.org/10.1021/acscombsci.5b00194
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000377925500008
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84974559593
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