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

  • Author(s): Visperas, Patrick R;
  • Wilson, Christopher G;
  • Winger, Jonathan A;
  • Yan, Qingrong;
  • Lin, Kevin;
  • Arkin, Michelle R;
  • Weiss, Arthur;
  • Kuriyan, John
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5491343/
No data is associated with this publication.
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. The screen is based on a fluorescence polarization assay for peptide binding to ZAP-70.

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