In silico screening and biological evaluation of inhibitors of Src-SH3 domain interaction with a proline-rich ligand.
Authors
Atatreh, NoorStojkoski, Cvetan
Smith, Phillippa
Booker, Grant W
Dive, Caroline
Frenkel, A David
Freeman, Sally
Bryce, Richard A
Affiliation
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PT, UK.Issue Date
2008-02-01
Metadata
Show full item recordAbstract
Src 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.Citation
In 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.Journal
Bioorganic & Medicinal Chemistry LettersDOI
10.1016/j.bmcl.2007.11.115PubMed ID
18083027Type
ArticleLanguage
enISSN
1464-3405ae974a485f413a2113503eed53cd6c53
10.1016/j.bmcl.2007.11.115