Title

Efficient Chemoenzymatic Synthesis of an N-glycan Isomer Library

Authors

Lei Li, Georgia State UniversityFollow
Yunpeng Liu, Georgia State UniversityFollow
Cheng Ma, Georgia State UniversityFollow
Jingyao Qu, Georgia State UniversityFollow
Angie D. Calderon, Georgia State UniversityFollow
Baolin Wu, Chemily Glycoscience
Na Wei, Georgia State University
Xuan Wang, Georgia State University
Yuxi Guo, Georgia State UniversityFollow
Zhongying Xiao, Georgia State UniversityFollow
Jing Song, Georgia State UniversityFollow
Go Sugiarto, University of California, Davis
Yanhong Li, University of California, DavisFollow
Hai Yu, University of California, DavisFollow
Xi Chen, University of California, DavisFollow
Peng George Wang, Georgia State UniversityFollow

Document Type

Article

Publication Date

2015

Abstract

Quantification, characterization and biofunctional studies of N-glycans on proteins remain challenging tasks due to the complexity, diversity and low abundance of these glycans. The availability of structurally defined N-glycan (especially isomer) libraries is essential to help solve these tasks. We report herein an efficient chemoenzymatic strategy, namely Core Synthesis/Enzymatic Extension (CSEE), for rapid production of diverse N-glycans. Starting with 5 chemically prepared building blocks, 8 N-glycan core structures containing one or two terminal N-acetyl-D-glucosamine (GlcNAc) residue(s) were chemically synthesized via consistent use of oligosaccharyl thioethers as glycosylation donors in a convergent fragment coupling strategy. Each of these core structures was then extended to 5 to 15 N-glycan sequences by enzymatic reactions catalyzed by 4 robust glycosyltransferases. Success in synthesizing N-glycans with Neu5Gc and core-fucosylation further expanded the ability of the enzymatic extension. Meanwhile, high performance liquid chromatography with an amide column enabled rapid and efficient purification (>98% purity) of N-glycans in milligram scales. A total of 73 N-glycans (63 isomers) were successfully prepared and characterized by MS2 and NMR. In summary, the CSEE strategy provides a practical approach for “mass production” of structurally defined N-glycans, which are important standards and probes for glycoscience.

Comments

Originally Published in:

Chem Sci, 6 (10), 5652-5661. DOI: 10.1039/c5sc02025e

Recommended Citation

Li, Lei; Liu, Yunpeng; Ma, Cheng; Qu, Jingyao; Calderon, Angie D.; Wu, Baolin; Wei, Na; Wang, Xuan; Guo, Yuxi; Xiao, Zhongying; Song, Jing; Sugiarto, Go; Li, Yanhong; Yu, Hai; Chen, Xi; and Wang, Peng George, "Efficient Chemoenzymatic Synthesis of an N-glycan Isomer Library" (2015). Chemistry Faculty Publications. 12.
https://scholarworks.gsu.edu/chemistry_facpub/12

Creative Commons License

This work is licensed under a Creative Commons Attribution-Noncommercial 3.0 License