دورية
Identification and Specificity Studies of Small-Molecule Ligands for SH3 Protein Domains
| العنوان: | Identification and Specificity Studies of Small-Molecule Ligands for SH3 Protein Domains |
|---|---|
| المؤلفون: | Inglis, S. R., Stojkoski, C., Branson, K. M., Cawthray, J. F., Fritz, D., Wiadrowski, E., Pyke, S. M., Booker, G. W. |
| المصدر: | Journal of Medicinal Chemistry; October 2004, Vol. 47 Issue: 22 p5405-5417, 13p |
| مستخلص: | The Src Homology 3 (SH3) domains are small protein−protein interaction domains that bind proline-rich sequences and mediate a wide range of cell-signaling and other important biological processes. Since deregulated signaling pathways form the basis of many human diseases, the SH3 domains have been attractive targets for novel therapeutics. High-affinity ligands for SH3 domains have been designed; however, these have all been peptide-based and no examples of entirely nonpeptide SH3 ligands have previously been reported. Using the mouse Tec Kinase SH3 domain as a model system for structure-based ligand design, we have identified several simple heterocyclic compounds that selectively bind to the Tec SH3 domain. Using a combination of nuclear magnetic resonance chemical shift perturbation, structure−activity relationships, and site-directed mutagenesis, the binding of these compounds at the proline-rich peptide-binding site has been characterized. The most potent of these, 2-aminoquinoline, bound with K |
| قاعدة البيانات: | Supplemental Index |
Find this issue from the American Chemical Society كن أول من يترك تعليقا!