Deglycase-activity oriented screening to identify DJ-1 inhibitors Journal Article


Authors: Maksimovic, I.; Finkin-Groner, E.; Fukase, Y.; Zheng, Q.; Sun, S.; Michino, M.; Huggins, D. J.; Myers, R. W.; David, Y.
Article Title: Deglycase-activity oriented screening to identify DJ-1 inhibitors
Abstract: The oncoprotein and Parkinson's disease-associated enzyme DJ-1/PARK7 has emerged as a promiscuous deglycase that can remove methylglyoxal-induced glycation adducts from both proteins and nucleotides. However, dissecting its structural and enzymatic functions remains a challenge due to the lack of potent, specific, and pharmacokinetically stable inhibitors targeting its catalytic site (including Cys106). To evaluate potential drug-like leads against DJ-1, we leveraged its deglycase activity in an enzyme-coupled, fluorescence lactate-detection assay based on the recent understanding of its deglycation mechanism. In addition, we developed assays to directly evaluate DJ-1's esterase activity using both colorimetric and fluorescent substrates. The resulting optimized assay was used to evaluate a library of potential reversible and irreversible DJ-1 inhibitors. The deglycase activity-oriented screening strategy described herein establishes a new platform for the discovery of potential anti-cancer drugs. © The Royal Society of Chemistry 2021.
Journal Title: RSC Medicinal Chemistry
Volume: 12
Issue: 7
ISSN: 2632-8682
Publisher: Royal Society of Chemistry  
Date Published: 2021-07-01
Start Page: 1232
End Page: 1238
Language: English
DOI: 10.1039/d1md00062d
PROVIDER: scopus
PMCID: PMC8292988
PUBMED: 34355187
DOI/URL:
Notes: Article -- Export Date: 1 September 2021 -- Source: Scopus
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  1. Qingfei Zheng
    8 Zheng