Small-Molecule Modulation of Protein Lipidation: From Chemical Probes to Therapeutics

Zhen Wang; Jiafu Ying; Xuanpu Zhang; Chen Miao; Yu Xiao; Jie Zou; Baoen Chen

doi:10.1002/cbic.202300071

Small-Molecule Modulation of Protein Lipidation: From Chemical Probes to Therapeutics

Chembiochem. 2023 Jul 17;24(14):e202300071. doi: 10.1002/cbic.202300071. Epub 2023 Jun 28.

Authors

Zhen Wang^{1

2}, Jiafu Ying^{1

2}, Xuanpu Zhang^{1

2}, Chen Miao^{1

2}, Yu Xiao^{1

2}, Jie Zou^{1

3}, Baoen Chen^{1

2}

Affiliations

¹ Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, P. R. China.
² ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311215, P. R. China.
³ College of Life Sciences, Zhejiang University, Hangzhou, 310058, P. R. China.

PMID: 37059689
DOI: 10.1002/cbic.202300071

Abstract

Protein lipidation is a widespread modification that regulates protein subcellular localization, structure and function. Dysregulation of protein lipidation has been implicated in various human diseases, including neurological disorders, infectious diseases and cancers. Thus lipid-modifying enzymes and their substrate proteins are emerging as attractive drug targets. The development of small-molecule modulators of protein lipidation has remarkably impacted our understanding of lipid-modification biology and potential therapeutics. In this review, we summarize recent progress in small-molecule targeting of protein lipidation and highlight therapeutic opportunities.

Keywords: inhibitors; protein lipidation; small molecules; therapeutics; transferases.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Drug Delivery Systems
Humans
Lipid Metabolism*
Lipids / chemistry
Protein Processing, Post-Translational
Proteins* / chemistry

Substances

Proteins
Lipids