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

• Ngôn ngữ: eng
• Ký hiệu phân loại: 636.7 Dogs
• Thông tin xuất bản: Berkeley, Calif. : Oak Ridge, Tenn. : Lawrence Berkeley National Laboratory ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2016
• Mô tả vật lý: Size: p. 324-331 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260930
• Chủ đề: 1. 60 applied life sciences; 2. Covalent inhibitor; 3. Fluorescence polarization (fp); 4. Kinase; 5. T cell; 6. Time-resolved fluorescence resonance energy transfer (tr-fret); 7. Zap-70

Tóm tắt

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 ?-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.