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

P. R. Visperas,Christopher G. Wilson,Jonathan A. Winger,Q. Yan,Kevin Lin,M. Arkin,A. Weiss,J. Kuriyan

Published 2017 in SLAS discovery : advancing life sciences R & D

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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