Development and Synthesis of Activity-based and Affinity-based Ubiquitin Probes
10.16476/j.pibb.2023.0119
- VernacularTitle:基于活性和亲和性的泛素探针的发展与合成
- Author:
Ling XU
1
;
Cui-Na WEI
1
;
Xian-Fu LU
1
;
Yi-Ming LI
2
Author Information
1. The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
2. Engineering Research Center of Bio-process, Ministry of Education, School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China
- Publication Type:Journal Article
- Keywords:
ubiquitin;
activity;
affinity;
probe;
chemical synthesis
- From:
Progress in Biochemistry and Biophysics
2024;51(3):598-623
- CountryChina
- Language:Chinese
-
Abstract:
Ubiquitination, a diverse post-translational modification, is carried out by enzymes including E1-activating enzymes, E2-conjugating enzymes, E3 ligases, and deubiquitinating enzymes (DUBs). Ubiquitin itself possesses 7 lysine residues and N-terminal methionine, allowing for the formation of polyubiquitin chains with different lengths and linkages. These chains exhibit various topologies that can be recognized by proteins containing ubiquitin-binding domain, thereby transmitting distinct cellular signals. To unravel the physiological mechanisms associated with ubiquitin, numerous ubiquitin probes have been developed. This review provides an overview of recent advancements in the field of ubiquitin probes, focusing on activity-based and affinity-based probes. Activity-based probes are designed to covalently bind to DUBs, E1s, or E3s, enabling the identification and characterization of these enzymes. Affinity-based probes, on the other hand, selectively bind to ubiquitin-binding domains, facilitating the identification of proteins that interact with ubiquitin. Moreover, this review comprehensively discusses the synthetic methodologies employed for the acquisition of ubiquitin probes. These includes meticulous discussions on the synthesis of individual monomeric modules, the establishment of isopeptide linkages, as well as the incorporation of reactive functional groups. Additionally, the review explores the emerging area of cell-penetrating ubiquitin probes and highlights their latest applications in living cells. These probes incorporate cell-penetrating peptides to enable their internalization into cells, allowing for direct visualization and manipulation of ubiquitin-modified proteins within their native environment. Overall, this review offers insights into the design, synthesis, and applications of ubiquitin probes, highlighting their significance in elucidating ubiquitin-mediated cellular processes.
