Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors

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dc.citation.journalTitleChemical Scienceen_US
dc.contributor.authorVohidov, Farrukhen_US
dc.contributor.authorKnudsen, Sarah E.en_US
dc.contributor.authorLeonard, Paul G.en_US
dc.contributor.authorOhata, Junen_US
dc.contributor.authorWheadon, Michael J.en_US
dc.contributor.authorPopp, Brian V.en_US
dc.contributor.authorLadbury, John E.en_US
dc.contributor.authorBall, Zachary T.en_US
dc.date.accessioned2015-06-15T18:57:49Zen_US
dc.date.available2015-06-15T18:57:49Zen_US
dc.date.issued2015en_US
dc.description.abstractSrc-family kinases (SFKs) play important roles in human biology and are key drug targets as well. However, achieving selective inhibition of individual Src-family kinases is challenging due to the high similarity within the protein family. We describe rhodium(II) conjugates that deliver both potent and selective inhibition of Src-family SH3 domains. Rhodium(II) conjugates offer dramatic affinity enhancements due to interactions with specific and unique Lewis-basic histidine residues near the SH3 binding interface, allowing predictable, structure-guided inhibition of SH3 targets that are recalcitrant to traditional inhibitors. In one example, a simple metallopeptide binds the Lyn SH3 domain with 6 nM affinity and exhibits functional activation of Lyn kinase under biologically relevant concentrations (EC50 200 nM).en_US
dc.identifier.citationVohidov, Farrukh, Knudsen, Sarah E., Leonard, Paul G., et al.. "Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors." <i>Chemical Science,</i> (2015) Royal Society of Chemistry: http://dx.doi.org/10.1039/C5SC01602A.en_US
dc.identifier.doihttp://dx.doi.org/10.1039/C5SC01602Aen_US
dc.identifier.urihttps://hdl.handle.net/1911/80753en_US
dc.language.isoengen_US
dc.publisherRoyal Society of Chemistryen_US
dc.rightsThis Open Access Article is licensed under a Creative Commons Attribution 3.0 Unported Licenceen_US
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/en_US
dc.titlePotent and selective inhibition of SH3 domains with dirhodium metalloinhibitorsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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