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In silico screening and biological evaluation of inhibitors of Src-SH3 domain interaction with a proline-rich ligand.
Atatreh, Noor Stojkoski, Cvetan Smith, Phillippa Booker, Grant W Dive, Caroline Frenkel, A David Freeman, Sally Bryce, Richard A
Atatreh, Noor
Stojkoski, Cvetan
Smith, Phillippa
Booker, Grant W
Dive, Caroline
Frenkel, A David
Freeman, Sally
Bryce, Richard A
Citations
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Abstract
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.
Description
Date
2008-02-01
Publisher
Keywords
Virtual Screening
Src
Inhibitors
Src
Inhibitors
Type
Article
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.