1. Optimization of Phosphotyrosine Peptides that Target the SH2 Domain of SOCS1 and Block Substrate Ubiquitination
- Author
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Hao Chen, Yuntong Wu, Kunlun Li, Iain Currie, Narelle Keating, Farhad Dehkhoda, Christoph Grohmann, Jeffrey J. Babon, Sandra E. Nicholson, and Brad E. Sleebs
- Subjects
src Homology Domains ,Suppressor of Cytokine Signaling 1 Protein ,Ubiquitination ,Molecular Medicine ,Suppressor of Cytokine Signaling Proteins ,General Medicine ,Phosphotyrosine ,Biochemistry - Abstract
Suppressor of cytokine signaling 1 (SOCS1) has emerged as a potential therapeutic target in inflammatory and viral diseases. SOCS1 operates via its kinase inhibitory region, Src homology 2 (SH2) domain, and SOCS box to negatively regulate the Janus kinase/signal transducers and activators of transcription signaling pathway. In this study, we utilized native phosphotyrosine peptide substrates as a starting point to iteratively explore the requirement of each amino acid position to target the SH2 domain of SOCS1. We show that Met, Thr, Thr, Val, and Asp in the respective -1, +1, +2, +3, and +5 positions within the peptide substrate are favored for binding to the SOCS1-SH2 domain and identifying several phosphotyrosine peptides that have potent SOCS1 binding affinity with IC
- Published
- 2022
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