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Discovery of a small-molecule inhibitor of protein-microRNA interaction using binding assay with a site-specifically labeled Lin28
Cited 47 time in
Web of Science
Cited 49 time in Scopus
- Authors
- Issue Date
- 2016-10
- Publisher
- American Chemical Society
- Citation
- Journal of the American Chemical Society, Vol.138 No.41, pp.13630-13638
- Abstract
- MicroRNAs (miRNAs) regulate gene expression by targeting protein-coding transcripts that are involved in various cellular processes. Thus, miRNA biogenesis has been recognized as a novel therapeutic target. Especially, the let-7 miRNA family is well-known for its tumor suppressor functions and is downregulated in many cancer cells. Lin28 protein binds to let-7 miRNA precursors to inhibit their maturation. Herein, we developed a FRET-based, high-throughput screening system to identify small-molecule inhibitors of the Lin28 let-7 interaction. We employed unnatural amino acid mutagenesis and bioorthogonal chemistry for the site-specific fluorescent labeling of Lin28, which ensures the robustness and reliability of the FRET-based protein miRNA binding assay. Using this direct binding assay,, we identified an inhibitor of the oncogenic Lin28 let-7 interaction. The inhibitor enhanced the production of let-7 miRNAs in Lin28-expressing cancer cells and reduced the level of let-7 target oncogene products.
- ISSN
- 0002-7863
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