2023
DOI: 10.1101/2023.12.18.572199
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Covalent Targeting of Splicing in T Cells

Kevin A. Scott,
Hiroyuki Kojima,
Nathalie Ropek
et al.

Abstract: SummaryDespite significant interest in therapeutic targeting of splicing, few chemical probes are available for the proteins involved in splicing. Here, we show that elaborated stereoisomeric acrylamide chemical probe EV96 and its analogues lead to a selective T cell state-dependent loss of interleukin 2-inducible T cell kinase (ITK) by targeting one of the core splicing factors SF3B1. Mechanistic investigations suggest that the state-dependency stems from a combination of differential protein turnover rates a… Show more

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