Chemoenzymatic Labeling, Detection and Profiling of Core Fucosylation in Live Cells

Zhu, Qiang1; Chaubard, Jean-Luc2; Geng, Didi1; Shen, Jiechen3; Ban, Lan2; Cheung, Sheldon T.2; Wei, Fangyu4; Liu, Yating4; Sun, Haofan5; Calderon, Angie6; Dong, Wenbo3; Qin, Weijie5; Li, Tiehai4; Wen, Liuqing4; Wang, Peng George6; Sun, Shisheng3; Yi, Wen1; Hsieh-Wilson, Linda C.2

2024-09-01

10.1021/jacs.4c09303

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY   影响因子和分区

0002-7863

1520-5126

Core fucosylation, the attachment of an alpha-1,6-linked-fucose to the N-glycan core pentasaccharide, is an abundant protein modification that plays critical roles in various biological processes such as cell signaling, B cell development, antibody-dependent cellular cytotoxicity, and oncogenesis. However, the tools currently used to detect core fucosylation suffer from poor specificity, exhibiting cross-reactivity against all types of fucosylation. Herein we report the development of a new chemoenzymatic strategy for the rapid and selective detection of core fucosylated glycans. This approach employs a galactosyltransferase enzyme identified fromCaenorhabditis elegansthat specifically transfers an azido-appended galactose residue onto core fucose via a beta-1,4 glycosidic linkage. We demonstrate that the approach exhibits superior specificity toward core fucose on a variety of complex N-glycans. The method enables detection of core fucosylated glycoproteins from complex cell lysates, as well as on live cell surfaces, and it can be integrated into a diagnostic platform to profile protein-specific core fucosylation levels. This chemoenzymatic labeling approach offers a new strategy for the identification of disease biomarkers and will allow researchers to further characterize the fundamental role of this important glycan in normal and disease physiology.

SCI

英语

其他

National Institutes of Health["R01 AG060540","AG062324"] ; National Natural Science Foundation of China (NSFC)["22325704","32271331","92353303","32201045","32471327","22007092"] ; Lingang Laboratory[LG-QS-202206-08] ; Fundamental Research Funds for Central Universities[K20220228]

Chemistry

Chemistry, Multidisciplinary

WOS:001314297700001

AMER CHEMICAL SOC

Web of Science

1.Zhejiang Univ, Coll Life Sci, Hangzhou 310012, Peoples R China
2.CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA
3.Northwest Univ, Coll Life Sci, Xian 710069, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Carbohydrate Based Drug Res Ctr, Shanghai 201203, Peoples R China
5.Natl Ctr Prot Sci Beijing, Beijing Inst Life, State Key Lab Proteom, Beijing 102206, Peoples R China
6.Southern Univ Sci & Technol, Sch Med, Dept Pharmacol, Shenzhen 518055, Guangdong, Peoples R China

Zhu, Qiang,Chaubard, Jean-Luc,Geng, Didi,et al. Chemoenzymatic Labeling, Detection and Profiling of Core Fucosylation in Live Cells[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2024.

Zhu, Qiang.,Chaubard, Jean-Luc.,Geng, Didi.,Shen, Jiechen.,Ban, Lan.,...&Hsieh-Wilson, Linda C..(2024).Chemoenzymatic Labeling, Detection and Profiling of Core Fucosylation in Live Cells.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY.

Zhu, Qiang,et al."Chemoenzymatic Labeling, Detection and Profiling of Core Fucosylation in Live Cells".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2024).