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Updated: Jul 16, 2026

Hierarchical and Programmable One-Pot Oligosaccharide Synthesis
Published on: September 6, 2019
Metabolic oligosaccharide engineering: perspectives, applications, and future directions.
Christopher T Campbell1, Srinivasa-Gopalan Sampathkumar, Kevin J Yarema
1Department of Biomedical Engineering, The Johns Hopkins University, Clark Hall 106A, Baltimore, MD 21218, USA.
Metabolic oligosaccharide engineering enables precise control over cell surface sugars, impacting development and disease. This approach uses non-natural sugars to modify cellular functions and create chemical tags for applications like drug delivery.
Area of Science:
- Glycobiology
- Chemical Biology
- Molecular Biology
Background:
- Oligosaccharides on cell surface molecules regulate critical biological processes.
- Glycosylation pathways are essential for protein and lipid modification.
- Limited technologies previously existed to manipulate glycosylation.
Purpose of the Study:
- To introduce and explore metabolic oligosaccharide engineering as a method to manipulate cellular glycosylation.
- To demonstrate the incorporation of non-natural sugars into cell surface glycoconjugates.
- To highlight the potential of engineered glycoconjugates for various applications.
Main Methods:
- Supplementing cells with exogenous non-natural sugars to intercept biosynthetic pathways.
- Utilizing enzymes' ability to process slightly altered metabolite structures.
- Incorporating reactive functional groups (ketones, azides, thiols) into glycoconjugates.
Main Results:
- Non-natural forms of sialic acid, GalNAc, GlcNAc, and fucose were successfully incorporated into cell surface glycoconjugates.
- O-GlcNAc protein modification was tagged using modified sugars.
- Engineered glycoconjugates with reactive tags were created for applications like drug delivery and controlled cell adhesion.
Conclusions:
- Metabolic oligosaccharide engineering offers a powerful new approach to manipulate glycosylation.
- This technology allows for the creation of functionalized glycoconjugates with diverse applications.
- Further engineering of non-natural sugars can enhance pharmacological properties and biological activities.
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