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dc.contributor.authorVohidov, Farrukh
Knudsen, Sarah E.
Leonard, Paul G.
Ohata, Jun
Wheadon, Michael J.
Popp, Brian V.
Ladbury, John E.
Ball, Zachary T.
dc.date.accessioned 2015-06-15T18:57:49Z
dc.date.available 2015-06-15T18:57:49Z
dc.date.issued 2015
dc.identifier.citation Vohidov, Farrukh, Knudsen, Sarah E., Leonard, Paul G., et al.. "Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors." Chemical Science, (2015) Royal Society of Chemistry: http://dx.doi.org/10.1039/C5SC01602A.
dc.identifier.urihttps://hdl.handle.net/1911/80753
dc.description.abstract Src-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).
dc.language.iso eng
dc.publisher Royal Society of Chemistry
dc.rights This Open Access Article is licensed under a Creative Commons Attribution 3.0 Unported Licence
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/
dc.title Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors
dc.type Journal article
dc.contributor.funder National Science Foundation
dc.contributor.funder Welch Foundation
dc.citation.journalTitle Chemical Science
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1039/C5SC01602A
dc.identifier.grantID CHE1055569 (National Science Foundation)
dc.identifier.grantID C-1680 (Welch Foundation)
dc.type.publication publisher version


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This Open Access Article is licensed under a Creative Commons Attribution 3.0 Unported Licence
Except where otherwise noted, this item's license is described as This Open Access Article is licensed under a Creative Commons Attribution 3.0 Unported Licence