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ID: ALA4052809

Journal: Bioorg Med Chem Lett

Title: Development of a highly reliable assay for ubiquitin-specific protease 2 inhibitors.

Authors: Wang Z, Xie W, Zhu M, Zhou H.

Abstract: The dynamic modification of proteins with ubiquitin plays crucial roles in major celluar functions, and is associated with a number of pathological conditions. Ubiquitin-specific proteases (USPs) cleave ubiquitin from substrate proteins, and rescue them from proteasomal degradation. Among them, USP2 is overexpressed and plays important roles in various cancers including prostate cancer. Thus, it represents an attractive target for drug discovery. In order to develop potent and selective USP2 inhibitors, a highly reliable assay is needed for in-depth structure-activity relationship study. We report the cloning, expression, and purification of USP2 and UBA52, and the development of a highly reliable assay based on readily available SDS-PAGE-Coomassie systeme using UBA52 as the substrate protein. A number of effective USP2 inhibitors were also identified using this assay.

CiteXplore: 28778469

DOI: 10.1016/j.bmcl.2017.07.059