Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen

Visperas, Patrick R.; Wilson, Christopher G.; Winger, Jonathan A.; Yan, Qingrong; Lin, Kevin; Arkin, Michelle R.; Weiss, Arthur; Kuriyan, John

doi:10.1177/1087057116681407

Title: Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen

Abstract

ZAP-70 is a critical molecule in the transduction of T cell antigen receptor signaling and the activation of T cells. Upon activation of the T cell antigen receptor, ZAP-70 is recruited to the intracellular ζ-chains of the T cell receptor, where ZAP-70 is activated and colocalized with its substrates. Inhibitors of ZAP-70 could potentially function as treatments for autoimmune diseases or organ transplantation. In this work, we present the design, optimization, and implementation of a screen for inhibitors that would disrupt the interaction between ZAP-70 and the T cell antigen receptor. Finally, the screen is based on a fluorescence polarization assay for peptide binding to ZAP-70.

Authors:

Visperas, Patrick R. ^[1]; Wilson, Christopher G. ^[2]; Winger, Jonathan A. ^[1]; Yan, Qingrong ^[1]; Lin, Kevin ^[1]; Arkin, Michelle R. ^[2]; Weiss, Arthur ^[3]; Kuriyan, John ^[4]

Univ. of California, Berkeley, CA (United States). California Inst. of Quantitative Biosciences and Howard Hughes Medical Inst., Dept. of Molecular and Cell Biology and Department of Chemistry
Univ. of California, San Francisco, CA (United States). Small Molecule Discovery Center, Dept. of Pharmaceutical Chemistry
Univ. of California, San Francisco, CA (United States). Rosalind Russell and Ephrain P. Engleman Rheumatology Research Center for Arthritis and Howard Hughes Medical Inst., Dept. of Medicine
Univ. of California, Berkeley, CA (United States). California Inst. of Quantitative Biosciences and Howard Hughes Medical Inst., Dept. of Molecular and Cell Biology and Department of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division

Publication Date:: Tue Dec 13 00:00:00 EST 2016

Research Org.:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Org.:: USDOE; National Institutes of Health (NIH)

OSTI Identifier:: 1379661

Grant/Contract Number:: AC02-05CH11231

Resource Type:: Accepted Manuscript

Journal Name:: SLAS DISCOVERY: Advancing Life Sciences R&D

Additional Journal Information:: Journal Volume: 22; Journal Issue: 3; Journal ID: ISSN 2472-5552

Publisher:: SAGE

Country of Publication:: United States

Language:: English

Subject:: 60 APPLIED LIFE SCIENCES; T cell; ZAP-70; fluorescence polarization (FP); time-resolved fluorescence resonance energy transfer (TR-FRET); covalent inhibitor; kinase

Citation Formats


                    Visperas, Patrick R., Wilson, Christopher G., Winger, Jonathan A., Yan, Qingrong, Lin, Kevin, Arkin, Michelle R., Weiss, Arthur, and Kuriyan, John. Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen.  United States: N. p., 2016. 
Web.  doi:10.1177/1087057116681407.

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                    Visperas, Patrick R., Wilson, Christopher G., Winger, Jonathan A., Yan, Qingrong, Lin, Kevin, Arkin, Michelle R., Weiss, Arthur, & Kuriyan, John. Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen.  United States.  https://doi.org/10.1177/1087057116681407

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                    Visperas, Patrick R., Wilson, Christopher G., Winger, Jonathan A., Yan, Qingrong, Lin, Kevin, Arkin, Michelle R., Weiss, Arthur, and Kuriyan, John. Tue .  
"Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen".  United States.  https://doi.org/10.1177/1087057116681407.  https://www.osti.gov/servlets/purl/1379661.

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@article{osti_1379661,

  title        = {Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen},

  author       = {Visperas, Patrick R. and Wilson, Christopher G. and Winger, Jonathan A. and Yan, Qingrong and Lin, Kevin and Arkin, Michelle R. and Weiss, Arthur and Kuriyan, John},

  abstractNote = {ZAP-70 is a critical molecule in the transduction of T cell antigen receptor signaling and the activation of T cells. Upon activation of the T cell antigen receptor, ZAP-70 is recruited to the intracellular ζ-chains of the T cell receptor, where ZAP-70 is activated and colocalized with its substrates. Inhibitors of ZAP-70 could potentially function as treatments for autoimmune diseases or organ transplantation. In this work, we present the design, optimization, and implementation of a screen for inhibitors that would disrupt the interaction between ZAP-70 and the T cell antigen receptor. Finally, the screen is based on a fluorescence polarization assay for peptide binding to ZAP-70.},

  doi          = {10.1177/1087057116681407},

  journal      = {SLAS DISCOVERY: Advancing Life Sciences R&D},

  number       = 3,

  volume       = 22,

  place        = {United States},

  year         = {Tue Dec 13 00:00:00 EST 2016},

  month        = {Tue Dec 13 00:00:00 EST 2016}

}

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Works referenced in this record:

Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding
journal, December 2014

Visperas, Patrick R.; Winger, Jonathan A.; Horton, Timothy M.
Biochemical Journal, Vol. 465, Issue 1
DOI: 10.1042/BJ20140793

ZAP-70: An Essential Kinase in T-cell Signaling
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Wang, H.; Kadlecek, T. A.; Au-Yeung, B. B.
Cold Spring Harbor Perspectives in Biology, Vol. 2, Issue 5
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Structural Basis for the Inhibition of Tyrosine Kinase Activity of ZAP-70
journal, May 2007

Deindl, Sebastian; Kadlecek, Theresa A.; Brdicka, Tomas
Cell, Vol. 129, Issue 4
DOI: 10.1016/j.cell.2007.03.039

Structural Basis for Activation of ZAP-70 by Phosphorylation of the SH2-Kinase Linker
journal, March 2013

Yan, Q.; Barros, T.; Visperas, P. R.
Molecular and Cellular Biology, Vol. 33, Issue 11
DOI: 10.1128/MCB.01637-12

Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor
journal, September 1995

Hatada, Marcos H.; Lu, Xiaode; Laird, Ellen R.
Nature, Vol. 377, Issue 6544
DOI: 10.1038/377032a0

Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases
journal, February 1994

Iwashima, M.; Irving, B.; van Oers, N.
Science, Vol. 263, Issue 5150
DOI: 10.1126/science.7509083

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Title: Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen

Abstract

Citation Formats

Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding journal, December 2014

ZAP-70: An Essential Kinase in T-cell Signaling journal, May 2010

Structural Basis for the Inhibition of Tyrosine Kinase Activity of ZAP-70 journal, May 2007

Structural Basis for Activation of ZAP-70 by Phosphorylation of the SH2-Kinase Linker journal, March 2013

Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor journal, September 1995

Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases journal, February 1994

Modification by covalent reaction or oxidation of cysteine residues in the tandem-SH2 domains of ZAP-70 and Syk can block phosphopeptide binding
journal, December 2014

ZAP-70: An Essential Kinase in T-cell Signaling
journal, May 2010

Structural Basis for the Inhibition of Tyrosine Kinase Activity of ZAP-70
journal, May 2007

Structural Basis for Activation of ZAP-70 by Phosphorylation of the SH2-Kinase Linker
journal, March 2013

Molecular basis for interaction of the protein tyrosine kinase ZAP-70 with the T-cell receptor
journal, September 1995

Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases
journal, February 1994