7pa2 › Citations

Chemical Toolkit for PARK7: Potent, Selective, and High-Throughput.

Figure 1
Figure 2
Scheme 1
Jia Y, Kim RQ, Kooij R, Ovaa H, Sapmaz A, Geurink PP
OpenAccess logo J Med Chem (2022)
Cited: 8 times
EuropePMC logo PMID: 36149939

Abstract

The multifunctional human Parkinson's disease protein 7 (PARK7/DJ1) is an attractive therapeutic target due to its link with early-onset Parkinson's disease, upregulation in various cancers, and contribution to chemoresistance. However, only a few compounds have been identified to bind PARK7 due to the lack of a dedicated chemical toolbox. We report the creation of such a toolbox and showcase the application of each of its components. The selective PARK7 submicromolar inhibitor with a cyanimide reactive group covalently modifies the active site Cys106. Installment of different dyes onto the inhibitor delivered two PARK7 probes. The Rhodamine110 probe provides a high-throughput screening compatible FP assay, showcased by screening a compound library (8000 molecules). The SulfoCy5-equipped probe is a valuable tool to assess the effect of PARK7 inhibitors in a cell lysate. Our work creates new possibilities to explore PARK7 function in a physiologically relevant setting and develop new and improved PARK7 inhibitors.

Reviews - 7pa2 mentioned but not cited (1)

  1. Fluorinated Molecules and Nanotechnology: Future 'Avengers' against the Alzheimer's Disease? Dabur M, Loureiro JA, Pereira MC. Int J Mol Sci 21 E2989 (2020)

Articles - 7pa2 mentioned but not cited (5)

  1. Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-beta protein. Calabrese B, Shaked GM, Tabarean IV, Braga J, Koo EH, Halpain S. Mol Cell Neurosci 35 183-193 (2007)
  2. Aβ oligomers inhibit synapse remodelling necessary for memory consolidation. Freir DB, Fedriani R, Scully D, Smith IM, Selkoe DJ, Walsh DM, Regan CM. Neurobiol Aging 32 2211-2218 (2011)
  3. Mass spectrometric characterization of amyloid-β species in the 7PA2 cell model of Alzheimer's disease. Portelius E, Olsson M, Brinkmalm G, Rüetschi U, Mattsson N, Andreasson U, Gobom J, Brinkmalm A, Hölttä M, Blennow K, Zetterberg H. J Alzheimers Dis 33 85-93 (2013)
  4. The heat shock response is modulated by and interferes with toxic effects of scrapie prion protein and amyloid β. Resenberger UK, Müller V, Munter LM, Baier M, Multhaup G, Wilson MR, Winklhofer KF, Tatzelt J. J Biol Chem 287 43765-43776 (2012)
  5. Chemical Toolkit for PARK7: Potent, Selective, and High-Throughput. Jia Y, Kim RQ, Kooij R, Ovaa H, Sapmaz A, Geurink PP. J Med Chem 65 13288-13304 (2022)


Reviews citing this publication (1)

  1. Technologies for Direct Detection of Covalent Protein-Drug Adducts. Mons E, Kim RQ, Mulder MPC. Pharmaceuticals (Basel) 16 547 (2023)

Articles citing this publication (1)

  1. Identification of DOT1L inhibitor in a screen for factors that promote dopaminergic neuron survival. Cui J, Carey J, Reijo Pera RA. Front Aging Neurosci 14 1026468 (2022)


Quick links