Details

Autor(en) / Beteiligte

• Chu, Guo‐Chao
• Hua, Xiao
• Zuo, Chong
• Chen, Chen‐Chen
• Meng, Xian‐Bin
• Zhang, Zhongping
• Fu, Yao
• Shi, Jing
• Li, Yi‐Ming

Titel

Efficient Semi‐Synthesis of Atypical Ubiquitin Chains and Ubiquitin‐Based Probes Forged by Thioether Isopeptide Bonds

Ist Teil von

• Chemistry : a European journal, 2019-12, Vol.25 (72), p.16668-16675

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2019

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• The development of powerful and general methods to acquire ubiquitin (Ub) chains has prompted the deciphering of Ub‐mediated processes. Herein, the cysteine‐aminoethylation assisted chemical ubiquitination (CAACU) strategy is extended and improved to enable the efficient semi‐synthesis of atypical Ub chain analogues and Ub‐based probes. Combining the Cys aminoethylation and the auxiliary‐mediated protein ligation, several linkage‐ and length‐defined atypical Ub chains including di‐Ubs, K27C‐linked tri‐Ub, K11/K48C‐branched tri‐Ub, and even the SUMOlated Ub are successfully prepared from recombinantly expressed starting materials at about a 9–20 mg L−1 expression level. In addition, the utility of this strategy is demonstrated with the synthesis of a novel non‐hydrolyzable di‐Ub PA probe, which may provide a new useful tool for the mechanistic studies of deubiquitinase (DUB) recognition. Ubiquitin probes: The cysteine‐aminoethylation assisted chemical ubiquitination (CAACU) strategy is extended and improved to enable the efficient semi‐synthesis of atypical Ub chain analogues and Ub‐based probes (see scheme).