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dc.contributor.authorAtatreh, Noor
dc.contributor.authorStojkoski, Cvetan
dc.contributor.authorSmith, Phillippa
dc.contributor.authorBooker, Grant W
dc.contributor.authorDive, Caroline
dc.contributor.authorFrenkel, A David
dc.contributor.authorFreeman, Sally
dc.contributor.authorBryce, Richard A
dc.date.accessioned2009-05-22T13:05:12Z
dc.date.available2009-05-22T13:05:12Z
dc.date.issued2008-02-01
dc.identifier.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.en
dc.identifier.issn1464-3405
dc.identifier.pmid18083027
dc.identifier.doi10.1016/j.bmcl.2007.11.115
dc.identifier.urihttp://hdl.handle.net/10541/68795
dc.description.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.
dc.language.isoenen
dc.subjectVirtual Screeningen
dc.subjectSrcen
dc.subjectInhibitorsen
dc.subject.meshAmino Acid Sequence
dc.subject.meshCombinatorial Chemistry Techniques
dc.subject.meshCrystallography, X-Ray
dc.subject.meshDrug Screening Assays, Antitumor
dc.subject.meshModels, Molecular
dc.subject.meshProline
dc.subject.meshProtein Binding
dc.subject.meshProto-Oncogene Proteins pp60(c-src)
dc.subject.meshQuinolines
dc.subject.meshStructure-Activity Relationship
dc.titleIn silico screening and biological evaluation of inhibitors of Src-SH3 domain interaction with a proline-rich ligand.en
dc.typeArticleen
dc.contributor.departmentSchool of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester M13 9PT, UK.en
dc.identifier.journalBioorganic & Medicinal Chemistry Lettersen
html.description.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.


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