Main Menu (Mobile)- Block

Main Menu - Block

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

Our Research / Publications
janelia7_blocks-janelia7_biblio_header | block
Nature. 2002 Apr 11;416(6881):653-7. doi: 10.1038/416653a
View Article on
Dissecting glucose signalling with diversity-oriented synthesis and small-molecule microarrays. Sternson Lab
Kuruvilla FG, Shamji AF, Sternson SM, Hergenrother PJ, Schreiber SL
Note: Research in this publication was not performed at Janelia.
janelia7_blocks-janelia7_biblio_abstract | block

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 Nil1p. 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.

PMID: 11948353 [PubMed - indexed for MEDLINE]

node:body | entity_field
janelia7_blocks-janelia7_biblio_authors | block

Janelia Authors

Scott Sternson
janelia7_blocks-janelia7_biblio_tools | block