Practical Chemical Synthesis of Atypical Ubiquitin Chains by Using an Isopeptide‐Linked Ub Isomer

Chemical ubiquitination is an effective approach for accessing structurally defined, atypical ubiquitin (Ub) chains that are difficult to prepare by other techniques. Herein, we describe a strategy that uses a readily accessible premade isopeptide‐linked 76‐mer (isoUb), which has an N‐terminal Cys a...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2017-10, Vol.56 (43), p.13333-13337
Main Authors: Tang, Shan, Liang, Lu‐Jun, Si, Yan‐Yan, Gao, Shuai, Wang, Jia‐Xing, Liang, Jun, Mei, Ziqing, Zheng, Ji‐Shen, Liu, Lei
Format: Article
Language:English
Subjects:
Chain branching
Chains
Chemical synthesis
native chemical ligation
post-translational modifications
protein chemical synthesis
proteolysis
Ubiquitin
Ubiquitination
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Chemical ubiquitination is an effective approach for accessing structurally defined, atypical ubiquitin (Ub) chains that are difficult to prepare by other techniques. Herein, we describe a strategy that uses a readily accessible premade isopeptide‐linked 76‐mer (isoUb), which has an N‐terminal Cys and a C‐terminal hydrazide, as the key building block to assemble atypical Ub chains in a modular fashion. This method avoids the use of auxiliary‐modified Lys and instead employs the canonical and therefore more robust Cys‐based native chemical ligation technique. The efficiency and capacity of this isoUb‐based strategy is exemplified by the cost‐effective synthesis of several linkage‐ and length‐defined atypical Ub chains, including K27‐linked tetra‐Ub and K11/K48‐branched tri‐, tetra‐, penta‐, and hexa‐Ubs. All together now: Chemical protein synthesis enabled the generation of homogeneous atypical ubiquitin (Ub) chains that are difficult to prepare by other approaches. A ligation method mediated by an isopeptide‐linked Ub isomer was developed to assemble the Ub chains. In this approach, a premade isopeptide‐linked 76‐mer (isoUb) bearing an N‐terminal Cys and a C‐terminal hydrazide is the key building block.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201708067