JMC: Novel water-soluble "azolinium" selectively modifies lysine residues of peptides and proteins

Lysine is abundant in the human proteome (5.

Usually, the ε-amino of lysine is easy to protonate in the physiological environment, so it is very challenging

Recently, Li Bo, associate researcher of Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Researcher Zhu Weiliang, together with Professor Ge Guangbo of Shanghai University of Traditional Chinese Medicine, based on the method of post-amino modification in n-butanol solution previously developed by the team^[1].

The study showed that this novel water-soluble azolin ammonium compound can selectively modify peptides such as pramolin derivatives, octreotide and somaglutide backbone lysine residues, as well as two highly conserved lysine residues (K5 and K61) of the BS-CoV-2 3CL^pro of bovine serum albumin, and SARS-CoV-2 3CL^pro is inactivated due to covalent modification of lysine

In summary, a new class of water-soluble azalinium developed in this research can chemically and locus-selectively modify peptides, proteins and living cell protein lysine, which has potential application value

Figure 1: Lysine residues of water-soluble "azolinium" modified peptides and proteins and their application at the cellular level

The first authors of the paper are Sun Haiguo, a doctoral student at the Shanghai Institute of Medicine, and Xi Mengyu, a master's student at the Shanghai Institute of Medicine, and Jin Qiang, a doctoral student at The Shanghai University of Traditional Chinese Medicine, and the corresponding authors are Li Bo, associate researchers and Zhu Weiliang, and Professor

The development of the above water-soluble "azolinium" is based on the team's continuous research work on the structural optimization of berberine for more than ten years

Original link: https://doi.

References:

[1] Peng Liu, Bo Li,* Mengyu Xi, Zhaoqiang Chen, Haiguo Sun, Xiajuan Huan, Xuejun Xu, Yong Zhang, Kun Zou, Xiangrui Jiang, Zehong Miao, Jinggen Liu, Jingshan Shen, Kaixian Chen, Weiliang Zhu.

[2] Haiguo Sun,# Mengyu Xi,# Qiang Jin,# Zhengdan Zhu, Yani Zhang, Guihua Jia, Guanghao Zhu, Mengru Sun, Hongwei Zhang, Xuelian Ren, Yong Zhang, Zhijian Xu, He Huang, Jingshan Shen, Bo Li,* Guangbo Ge,* Kaixian Chen, Weiliang Zhu.

[3] Bo Li,# Gaihong Wang,# Mu Yang, Zhijian Xu, Bubing Zeng,* Heyao Wang,* Jingshan Shen, Kaixian Chen, Weiliang Zhu.

[4] Shuaikang Chang,# Bo Li,# Yongsheng Xie,# Yingcong Wang, Zhijian Xu, Shuhan Jin, Dandan Yu, Huaping Wang, Yumeng Lu, Yong Zhang, Ruye Ma, Cheng Huang, Weiming Lai, Xiaosong Wu, Weiliang Zhu,* Jumei Shi,* DCZ0014, a novel compound in the therapy of diffuse large B-cell lymphoma via the B cell receptor signaling pathway, Neoplasia, 2022, 24(1): 50-61.

[5] Bo Li,# Gaihong Wang,# Zhijian Xu, Yong Zhang, Xiangui Huang, Bubing Zeng, Kaixian Chen, Jiye Shi,* Heyao Wang,* Weiliang Zhu.

[6] Lu Gao,# Bo Li,# Guang Yang,# Peng Liu, Xiucai Lan, Shuaikang Chang, Yi Tao, Zhijian Xu, Bingqian Xie, Xi Sun, Yingcong Wang, Liangning Hu, Dandan Yu, Yongsheng Xie, Wenxuan Bu, Xiaosong Wu, Weiliang Zhu,* Jumei Shi.

[7] Lixia Ding,# Lu Wang,# Kun Zou,# Bo Li,* Yunqing Song, Qihua Zhang, Yitian Zhao, Zhijian Xu, Guangbo Ge,* Bo Zhao,* and Weiliang Zhu.

[8] Bo Li,# Susu Xue,# Yang Yang,# Jia Feng,# Peng Liu, Yong Zhang, Jianming Zhu, Zhijian Xu, Adrian Hall, Bo Zhao,* Jiye Shi,* and Weiliang Zhu.
* Regioselectivity and Mechanism of Synthesizing N-Substituted 2-Pyridones and 2-Substituted Pyridines via Metal-Free C-O and C-N Bond-Cleaving of Oxazoline[3,2-a]pyridiniums, Sci Rep.
2017, 7: 41287.

[9] Bo Li,# Heng Li,# Zhengdan Zhu,# Caigui Xiang, Zhijian Xu, Chen Fan, Yitian Zhao, Chunlan Feng, Haiguo Sun, Yong Zhang, Tingting Cai, Wei Tang,* Weiliang Zhu.
* Discovery of ChiralN-2’-aryletheryl-1’-alkoxy-ethyl substituted arylisoquinolones with anti-inflammatory activity from the nucleophilic addition reactions of the thiophenols and oxazolinium, Eur J Med Chem.
2021, 222: 113583.

(Contributed by: Zhu Weiliang's research group)