Conformational Stabilization of Ubiquitin Yields Potent and Selective Inhibitors of USP7

Zhang, Y, et al., 9(1), 51-8, Nat Chem Biol, 2013

Computational design along with phage display and affinity maturation were utilized to modify ubiquitin to select for variants with altered conformations resulting in high affinity binding to the USP7 tumor-associated deubiquitinase (DUB). High affinity clones were selected, providing tools for elucidating the role of USP7 in the Mdm2-p53 tumorigenic pathway. The Octet RED384 system and Streptavidin biosensors were used to determine binding affinities of ubiquitin variants to USP7 constructs.

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