Browsing by Author "Popp, Brian V."

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    Hybrid organic-inorganic inhibitors of a PDZ-peptide interaction that regulates CFTR endocytic fate
    (Wiley-VCH Verlag, 2012) Kundu, Rituparna; Cushing, Patrick R.; Popp, Brian V.; Zhao, Yu; Madden, Dean R.; Ball, Zachary T.
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    Potent and selective inhibition of SH3 domains with dirhodium metalloinhibitors
    (Royal Society of Chemistry, 2015) Vohidov, Farrukh; Knudsen, Sarah E.; Leonard, Paul G.; Ohata, Jun; Wheadon, Michael J.; Popp, Brian V.; Ladbury, John E.; Ball, Zachary T.
    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).
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    Small molecule conjugates with dimetal species for protein inhibition
    (2015-06-02) Ball, Zachary T.; Kundu, Rituparna; Popp, Brian V.; Madden, Dean R.; Cushing, Patrick R.; Rice University; Trustees of Dartmouth College; United States Patent and Trademark Office
    Methods for targeting a protein by providing an inhibitor covalently linked to a rhodium(II) complex, introducing the inhibitor to the target protein and allowing the inhibitor and protein to interact. The rhodium(II) complex covalently linked to the inhibitor binds the target protein both inorganically and organically and forms stabilizing secondary contacts between the rhodium(II) complex and the protein.