Dissecting glucose signalling with diversity-oriented synthesis and small-molecule microarrays

Finny G. Kuruvilla, Alykhan F. Shamji, Scott M. Sternson, Paul J. Hergenrother and Stuart L. Schreiber ()
Additional contact information
Finny G. Kuruvilla: Harvard University
Alykhan F. Shamji: Harvard University
Scott M. Sternson: Harvard University
Paul J. Hergenrother: Harvard University
Stuart L. Schreiber: Harvard University

Nature, 2002, vol. 416, issue 6881, 653-657

Abstract: Abstract Small molecules that alter protein function provide a means to modulate biological networks with temporal resolution. Here we demonstrate a potentially general and scalable method of identifying such molecules by application to a particular protein, Ure2p, which represses the transcription factors Gln3p and Nil1p1,2,3. By probing a high-density microarray of small molecules generated by diversity-oriented synthesis with fluorescently labelled Ure2p, we performed 3,780 protein-binding assays in parallel and identified several compounds that bind Ure2p. One compound, which we call uretupamine, specifically activates a glucose-sensitive transcriptional pathway downstream of Ure2p. Whole-genome transcription profiling and chemical epistasis demonstrate the remarkable Ure2p specificity of uretupamine and its ability to modulate the glucose-sensitive subset of genes downstream of Ure2p. These results demonstrate that diversity-oriented synthesis and small-molecule microarrays can be used to identify small molecules that bind to a protein of interest, and that these small molecules can regulate specific functions of the protein.

Date: 2002
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/416653a Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:416:y:2002:i:6881:d:10.1038_416653a

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/416653a

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().