Dissecting glucose signalling with diversity-oriented synthesis and small-molecule microarrays
Dissecting glucose signalling with diversity-oriented synthesis and small-molecule microarrays
复制标题
DOI：
10.1038/416653a
复制
发表时间：
2002-04-11
期刊：
影响因子：
64.8
通讯作者：
Schreiber, SL
中科院分区：
文献类型：
--
作者：
Kuruvilla, FG;Shamji, AF;Schreiber, SL
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.
