In silico screening and biological evaluation of inhibitors of Src-SH3 domain interaction with a proline-rich ligand.
Booker, Grant W
Frenkel, A David
Bryce, Richard A
AffiliationSchool of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PT, UK.
MetadataShow full item record
AbstractSrc signalling and transduction are directly involved in cell growth, cell cycle, malignant transformation and cell migration, providing therapeutic opportunities through inhibition of Src. Here we report virtual screening for novel compounds that inhibit the Src-SH3 protein-protein interaction with a proline-rich peptide ligand. Computational docking of the ZINC compound database was performed using GOLD. Top-scoring compounds were assayed using a fluorescence polarization-based assay. A benzoquinoline derivative showed micromolar inhibition of binding between Src-SH3 and the proline-rich peptide. Several analogues were subsequently assayed showing the requirement of a linker between the benzoquinoline and phenyl rings, and electron donating substituents on the phenyl ring.
CitationIn silico screening and biological evaluation of inhibitors of Src-SH3 domain interaction with a proline-rich ligand. 2008, 18 (3):1217-22 Bioorg. Med. Chem. Lett.
JournalBioorganic & Medicinal Chemistry Letters
- Crystal structure analysis and solution studies of human Lck-SH3; zinc-induced homodimerization competes with the binding of proline-rich motifs.
- Authors: Romir J, Lilie H, Egerer-Sieber C, Bauer F, Sticht H, Muller YA
- Issue date: 2007 Feb 2
- Binding of the proline-rich segment of myelin basic protein to SH3 domains: spectroscopic, microarray, and modeling studies of ligand conformation and effects of posttranslational modifications.
- Authors: Polverini E, Rangaraj G, Libich DS, Boggs JM, Harauz G
- Issue date: 2008 Jan 8
- The structure and interactions of the proline-rich domain of ASPP2.
- Authors: Rotem S, Katz C, Benyamini H, Lebendiker M, Veprintsev D, Rüdiger S, Danieli T, Friedler A
- Issue date: 2008 Jul 4
- Structure of EVH1, a novel proline-rich ligand-binding module involved in cytoskeletal dynamics and neural function.
- Authors: Fedorov AA, Fedorov E, Gertler F, Almo SC
- Issue date: 1999 Jul
- Identification and specificity studies of small-molecule ligands for SH3 protein domains.
- Authors: Inglis SR, Stojkoski C, Branson KM, Cawthray JF, Fritz D, Wiadrowski E, Pyke SM, Booker GW
- Issue date: 2004 Oct 21