Abstract
Active-site directed probes are powerful tools for studying the ubiquitin conjugation and deconjugation machinery. Branched ubiquitin chains have emerged as important proteasome-targeting signals for aggregation-prone proteins and cell cycle regulators. By implementing a new synthetic strategy for the electrophilic warhead, we herein report on the generation and reactivity of a series of branched triubiquitin active-site directed probes. These new tools can be used to dissect the molecular basis of branched chain assembly and disassembly.
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