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Metabolic Glycoengineering of Sialic Acid Using N-acyl-modified Mannosamines
Published on: November 25, 2017
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Metabolic Glycoengineering with N-Acyl Side Chain Modified Mannosamines
Paul R Wratil1, Rüdiger Horstkorte2, Werner Reutter3
1Institut für Laboratoriumsmedizin, Klinische Chemie und Pathobiochemie, Charité-Universitätsmedizin Berlin, Arnimallee 22, 14195, Berlin, Germany. paul-robin.wratil@charite.de.
Angewandte Chemie (International Ed. in English)
|July 21, 2016
Summary
Metabolic glycoengineering (MGE) uses unnatural sugars to modify cell glycans. This technique allows for visualizing cell surface sugars and has potential biological applications.
Area of Science:
- Biochemistry
- Cell Biology
- Glycobiology
Background:
- Metabolic glycoengineering (MGE) involves administering unnatural monosaccharide derivatives to cells or animals.
- These sugar analogs are metabolized and incorporated into newly synthesized glycoconjugates.
- The feasibility of MGE was initially demonstrated for sialylated glycans using N-acyl-modified mannosamines.
Purpose of the Study:
- To explore the potential of metabolic glycoengineering for modifying cell surface glycans.
- To investigate the enzyme tolerance of the Roseman-Warren biosynthetic pathway for unnatural sugar modifications.
- To highlight the applications of MGE in studying glycan topography and dynamics.
Main Methods:
- Treatment of cells or animals with unnatural monosaccharide derivatives.
- Metabolic processing of sugar analogs within the cytosol.
- Enzymatic incorporation of modified sugars into glycoconjugates.
- Utilizing N-acyl-modified mannosamines as precursors for unnatural sialic acids.
Main Results:
- Demonstrated the feasibility of MGE for sialylated glycans.
- Showcased the promiscuity of Roseman-Warren pathway enzymes, tolerating N-acyl side chain modifications.
- Incorporation of unnatural sialic acids into cellular and organ glycoconjugates.
- Aliphatic MGE led to biological consequences in treated cells.
- Bioorthogonal MGE enabled visualization of sialylated glycans in vitro, ex vivo, and in vivo.
Conclusions:
- Metabolic glycoengineering is a viable strategy for introducing unnatural modifications into cellular glycans.
- Enzyme tolerance within the Roseman-Warren pathway is crucial for successful MGE.
- MGE offers powerful tools for both fundamental biological studies and potential therapeutic applications.
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