Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics

Wang，Shuaishuai1; Chen，Congcong1,2,3; Gadi，Madhusudhan Reddy1; Saikam，Varma1; Liu，Ding1; Zhu，He1; Bollag，Roni4; Liu，Kebin5; Chen，Xi6; Wang，Fengshan7; Wang，Peng George1,9; Ling，Peixue2,3,7; Guan，Wanyi8; Li，Lei1

2021-12-01

10.1038/s41467-021-23428-x

Nature Communications   影响因子和分区

2041-1723

2041-1723

O-GalNAc glycans (or mucin O-glycans) play pivotal roles in diverse biological and pathological processes, including tumor growth and progression. Structurally defined O-GalNAc glycans are essential for functional studies but synthetic challenges and their inherent structural diversity and complexity have limited access to these compounds. Herein, we report an efficient and robust chemoenzymatic modular assembly (CEMA) strategy to construct structurally diverse O-GalNAc glycans. The key to this strategy is the convergent assembly of O-GalNAc cores 1–4 and 6 from three chemical building blocks, followed by enzymatic diversification of the cores by 13 well-tailored enzyme modules. A total of 83 O-GalNAc glycans presenting various natural glycan epitopes are obtained and used to generate a unique synthetic mucin O-glycan microarray. Binding specificities of glycan-binding proteins (GBPs) including plant lectins and selected anti-glycan antibodies towards these O-GalNAc glycans are revealed by this microarray, promoting their applicability in functional O-glycomics. Serum samples from colorectal cancer patients and healthy controls are assayed using the array reveal higher bindings towards less common cores 3, 4, and 6 than abundant cores 1 and 2, providing insights into O-GalNAc glycan structure-activity relationships.

SCI

英语

NI论文

通讯

National Institutes of Health["U01GM116263","U54HL142019","R44GM123820"]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000663756900004

NATURE RESEARCH

2-s2.0-85107796665

Scopus

1.Department of Chemistry,Georgia State University,Atlanta,30303,United States
2.National Glycoengineering Research Center,Shandong Provincial Key Laboratory of Glycochemistry and Glycobiology,Shandong University,Qingdao,266237,China
3.Shandong Academy of Pharmaceutical Science,Key Laboratory of Biopharmaceuticals,Engineering Laboratory of Polysaccharide Drugs,National-Local Joint Engineering Laboratory of Polysaccharide Drugs,Jinan,250101,China
4.Georgia Cancer Center,Augusta University,Augusta,30912,United States
5.Department of Biochemistry and Molecular Biology,Medical College of Georgia,Augusta,30912,United States
6.Department of Chemistry,University of California,Davis,95616,United States
7.Key Laboratory of Chemical Biology (Ministry of Education),Institute of Biochemical and Biotechnological Drug,School of Pharmaceutical Science,Shandong University,Jinan,250012,China
8.College of Life Science,Hebei Normal University,Shijiazhuang,050024,China
9.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China

Wang，Shuaishuai,Chen，Congcong,Gadi，Madhusudhan Reddy,et al. Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics[J]. Nature Communications,2021,12(1).

Wang，Shuaishuai.,Chen，Congcong.,Gadi，Madhusudhan Reddy.,Saikam，Varma.,Liu，Ding.,...&Li，Lei.(2021).Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics.Nature Communications,12(1).

Wang，Shuaishuai,et al."Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics".Nature Communications 12.1(2021).