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Chemical Probe To Monitor the Parkinsonism-Associated Protein DJ-1 in Live Cells.

Abstract：

:Reactive oxygen species (ROS) play an important role in the onset of Parkinson's disease (PD), and deciphering protective mechanisms is a major goal for therapeutic development. Here, DJ-1 (PARK7) gained major attention when a conserved cysteine residue with a putative role in oxidative stress sensing/protection was linked to PD. Inspired by previous studies with a bacterial homologue of DJ-1, several amino-epoxycylcohexenones were screened for enzyme inhibition, and a chemical probe with specificity for the human ortholog was selected for cellular studies. The probe selectively labeled the cysteine oxidation sensor and whole proteome analysis in HeLa, A549, and SHSY5Y cell lines confirmed strong enrichment of reduced DJ-1 as the most prominent target. Increasing levels of oxidative stress diminished this signal demonstrating the utility of our tool compound for selective in situ monitoring of this important biomarker in its reduced state.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Drechsel J,Mandl FA,Sieber SA

doi

10.1021/acschembio.8b00633

subject

Has Abstract

pub_date

2018-08-17 00:00:00

pages

2016-2019

issue

8

eissn

1554-8929

issn

1554-8937

journal_volume

13

pub_type

杂志文章

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