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Eberly College of Arts and Sciences




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).

Source Citation

Vohidov, F., Knudsen, S. E., Leonard, P. G., Ohata, J., Wheadon, M. J., Popp, B. V., Ladbury, J. E., & Ball, Z. T. (2015). Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors. Chemical Science, 6(8), 4778–4783.


This article is Open Access Creative Commons BY license All publication charges for this article have been paid for by the Royal Society of Chemistry



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