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Chemical Biology Tools for Protein Lysine Acylation

期刊

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202200303

关键词

Chemical Probes; Epigenetics; Lysine Acylation; PROTAC; Protein Machinery

资金

  1. National Natural Science Foundation of China [22107058, 32122003, 21778044, 81800645, 91949202, 91642204, 82090024, 82170734]
  2. Shandong Provincial Natural Science Foundation of China [ZR2019ZD40, ZR2019BH030]
  3. Synthetic Biology Research & Development Programme (SBP) of National Research Foundation, Singapore [SBP-P4, SBP-P8]
  4. Program of Qilu Young Scholars of Shandong University

向作者/读者索取更多资源

Lysine acylation plays pivotal roles in cell physiology and dysregulated lysine acylation is closely involved in the pathophysiological progress of many human diseases. Chemical biology tools have advanced the study of lysine acylation and its regulatory proteins, leading to the discovery of ligands for targeting regulators of lysine acylation. However, there are still challenges and a need for more discriminating chemical probes in future studies of post-translational modifications.
Lysine acylation plays pivotal roles in cell physiology, including DNA transcription and repair, signal transduction, immune defense, metabolism, and many other key cellular processes. Molecular mechanisms of dysregulated lysine acylation are closely involved in the pathophysiological progress of many human diseases, most notably cancers. In recent years, chemical biology tools have become instrumental in studying the function of post-translational modifications (PTMs), identifying new writers, erasers and readers, and in targeted therapies. Here, we describe key developments in chemical biology approaches that have advanced the study of lysine acylation and its regulatory proteins (2016-2021). We further discuss the discovery of ligands (inhibitors and PROTACs) that are capable of targeting regulators of lysine acylation. Next, we discuss some current challenges of these chemical biology probes and suggest how chemists and biologists can utilize chemical probes with more discriminating capacity. Finally, we suggest some critical considerations in future studies of PTMs from our perspective.

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