Recent advances in the chemical synthesis and semi-synthesis of poly-ubiquitin-based proteins and probes

  • Yun-Kun QiEmail author
  • Yan-Yan Si
  • Shan-Shan Du
  • Jun Liang
  • KeWei WangEmail author
  • Ji-Shen ZhengEmail author


Ubiquitination, a key and extensive posttranslational modification of proteins, has profound effects on a variety of physiological and pathological processes. The inherent complexity of ubiquitin conjugates makes it highly challenging to study the functional and structural mechanisms of ubiquitination. To address these challenges, accesses to sufficient poly-ubiquitin chains or ubiquitinated proteins are urgently needed. Over the last decade, synthetic protein chemists have developed several novel peptide ligation methods for the preparation of ubiquitin conjugates with precise control over the atomic structure. In this review, we summarize the recent breakthroughs and potential challenges in the chemical synthesis and semi-synthesis of ubiquitin conjugates with respect to the preparation of poly-ubiquitin-based proteins and ubiquitin-based probes.


ubiquitination poly-ubiquitin chains poly-ubiquitin-based proteins poly-ubiquitin-based probes chemical protein synthesis 


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This work was supported by the National Natural Science Foundation of China (21807063, 91753120, U1732161, 81503094), the start-up grant from Qingdao University (41118010086), and the China Postdoctoral Science Foundation (2016 M600524).


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Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medicinal Chemistry, School of PharmacyQingdao UniversityQingdaoChina
  2. 2.Institute of Innovative DrugsQingdao UniversityQingdaoChina
  3. 3.School of Life SciencesUniversity of Science and Technology of ChinaHefeiChina
  4. 4.State Key Laboratory Base for Eco-Chemical Engineering in College of Chemical EngineeringQingdao University of Science and TechnologyQingdaoChina

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