Development of sulfonium and diazonium tools to investigate lysine methylation
Date:2025-12-24

 

NO. 91

 

CIMR Wednesday Lecture Series

 

Time:

Wednesday, Dec. 24 2025, 4:00 p.m.

 

Location:

Multi-Function Hall, 2nd Floor, North Basic Research Building 

 

Host

Hanjie Jiang (姜汉杰)

Chinese Institutes for Medical Research, Beijing

 

Speaker

Mingxuan Wu (吴明轩)

Associate Professor

School of Science, Westlake University

 

TITLE:

Development of sulfonium and diazonium tools to investigate lysine methylation

 

ABSTRACT:

Lysine methylation is a posttranslational modification (PTM) that regulates many cellular processes. For example, histone H3K27 methylation leads to gene silence as an important type of epigenetic marks. Hypermethylation of histone H3K27 may drive cancer and the methyltransferase EZH2 is a hot drug target. Therefore, understanding of lysine methylation function is important to both basic and translational research. My lab aims to develop new chemical tools to study proteins that are involved in lysine methylation and identify novel lysine methylation sites. First, we developed nucleosome probes and sulfonium probes that enable selective crosslinking to methyllysine readers. New readers including PWWP4 and BWRD3 were identified from cellular samples. Second, we developed aryl diazonium agents that selectively crosslink monomethyllysine (Kme1) so that tryptic Kme1 peptides could be enriched for proteomic analysis. A record number of methyllysine sites were identified and a significant amount of SAM-independent lysine methylation was revealed. We hope the sulfonium and diazonium tools can be widely applied to expand our knowledge of lysine methylation.

 

SELECTED PAPERS

1. Feng, F.#; Gao, Y.#; Zhao, Q.#; Luo, T.; Yang, Q.; Zhao, N.; Xiao, Y.; Han, Y.; Pan, J.; Feng, S.; Zhang, L.; Wu, M.*, Single Electron Transfer between Sulfonium and Tryptophan Enables Site-selective Photo Crosslinking of Methyllysine Reader Proteins. Chem. 2024, 16, 1267-1277.

2. Yan, L.; Zheng, M.; Fan, M.; Yao, R.; Zou, K.; Feng, S.; Wu, M.*, A Chemo-selective Enrichment Strategy to Achieve In-depth Coverage of Methyllysine Proteome. Angew. Chem. Int. Ed. 2024, e202408564.