TY - JOUR
T1 - Chemoenzymatic modular assembly of O-GalNAc glycans for functional glycomics
AU - Wang, Shuaishuai
AU - Chen, Congcong
AU - Gadi, Madhusudhan Reddy
AU - Saikam, Varma
AU - Liu, Ding
AU - Zhu, He
AU - Bollag, Roni
AU - Liu, Kebin
AU - Chen, Xi
AU - Wang, Fengshan
AU - Wang, Peng George
AU - Ling, Peixue
AU - Guan, Wanyi
AU - Li, Lei
N1 - Funding Information:
This work was supported by National Institutes of Health (U01GM116263, U54HL142019, and R44GM123820). S.W. was partially supported by Molecular Basis for Disease (MBD) Doctoral Fellowship at Georgia State University. We thank Z biotech LLC (Aurora, CO) for microarray fabrication, and Dr. Xiu-Feng Wan (University of Missouri) for kindly providing recombinant HA proteins of H3N2 (A/Brisb-ane/10/ 2007) and H1N1 (A/New York/18/2009) (acquired from BEI resources).
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-021-23428-x
DO - 10.1038/s41467-021-23428-x
M3 - Article
C2 - 34117223
AN - SCOPUS:85107796665
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3573
ER -
