| | |  | | | | Record from Web of Science® | | | | | | |
| Dissecting glucose signalling with diversity-oriented synthesis and small-molecule microarrays |
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| Author(s): Kuruvilla FG, Shamji AF, Sternson SM, Hergenrother PJ, Schreiber SL |
| Source: NATURE Volume: 416 Issue: 6881 Pages: 653-657 Published: APR 11 2002 |
| Times Cited: 183 References: 28 |
| 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(1-3). 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Schreiber, SL (reprint author), Harvard Univ, Dept Chem & Biol Chem, Bauer Ctr Genom Res, Inst Chem & Cell Biol,Howard Hughes Med Inst, 12 Oxford St, Cambridge, MA 02138 USA |
Addresses:
1. Harvard Univ, Dept Chem & Biol Chem, Bauer Ctr Genom Res, Inst Chem & Cell Biol,Howard Hughes Med Inst, Cambridge, MA 02138 USA
2. Harvard Univ, Dept Biophys, Cambridge, MA 02138 USA |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 539YV |
| ISSN: 0028-0836 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |