Synthesis of Linkage-Specific Polyubiquitin Probes Using Unnatural Amino Acids.

Authors

Matthew T Buhl, T Ashton Cropp

Published in

Methods in molecular biology (Clifton, N.J.). Volume 3009. Pages 45-54.

Abstract

Activity-based probes based on polyubiquitin chains are powerful tools for studying ubiquitin-conjugating pathways and the substrate specificity of deubiquitinase (DUB) enzymes. These probes can be synthesized through a genetically encoded unnatural amino acid (UAA), N^ε-L-thiaprolyl-L-lysine (ThzK). This chapter details the chemical synthesis of ThzK and preparation of diUb probes, leveraging ThzK to enable the production of site-specifically installed isopeptide bonds. The resulting probes facilitate mechanistic studies of ubiquitination and deubiquitination specificity and have applications in understanding diseases associated with ubiquitination dysfunction.

PMID:
42542479
Bibliographic data and abstract were imported from PubMed on 02 Aug 2026.

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