Identification of Inhibitors of the Association of ZAP-70 with the T Cell Receptor by High-Throughput Screen. (March 2017)

• Record Type: Journal Article
• Authors: Visperas, Patrick R.; Wilson, Christopher G.; Winger, Jonathan A.; Yan, Qingrong; Lin, Kevin; Arkin, Michelle R.; Weiss, Arthur; Kuriyan, John
• Is Part Of: SLAS discovery. Volume 22:Number 3(2017)
• Page Start: 324
• Page End: 331
• Publication Date: 2017-03
• Subjects: T cell -- ZAP-70 -- fluorescence polarization (FP) -- time-resolved fluorescence resonance energy transfer (TR-FRET) -- covalent inhibitor -- kinase; Drugs -- Analysis -- Periodicals; Drugs -- Testing -- Periodicals; Biomolecules -- Analysis -- Periodicals; Biomolecules -- Analysis; Drugs -- Analysis; Drugs -- Testing; Drug Evaluation, Preclinical; Molecular Biology -- methods; Periodicals; Periodicals; 615.1
• DOI: 10.1177/1087057116681407
• Languages: English
• ISSNs: 2472-5552

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.