Enzymatic Sialylation of Synthetic Multivalent Scaffolds: From 3′‐Sialyllactose Glycomacromolecules to Novel Neoglycosides

Sialoglycans play a key role in many biological recognition processes and sialylated conjugates of various types have successfully been applied, e.g., as antivirals or in antitumor therapy. A key feature for high affinity binding of such conjugates is the multivalent presentation of sialoglycans whi...

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Bibliographic Details
Published in:Macromolecular bioscience 2022-12, Vol.22 (12), p.e2200358-n/a
Main Authors: Konietzny, Patrick B., Peters, Hannelore, Hofer, Marc L., Gerling‐Driessen, Ulla I. M., Vries, Robert P., Peters, Thomas, Hartmann, Laura
Format: Article
Language:English
Subjects:
Antiviral agents
Biological activity
Carbohydrates
Chemical synthesis
chemoenzymatic synthesis
Conjugates
glycomacromolecules
Macromolecules
neoglycoside
Oligosaccharides
Pasteurella multocida
Polymers
Scaffolds
sialic acid
solid phase polymer synthesis
Solid phases
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Summary:Sialoglycans play a key role in many biological recognition processes and sialylated conjugates of various types have successfully been applied, e.g., as antivirals or in antitumor therapy. A key feature for high affinity binding of such conjugates is the multivalent presentation of sialoglycans which often possess synthetic challenges. Here, the combination is described of solid phase polymer synthesis and enzymatic sialylation yielding 3′‐sialyllactose‐presenting precision glycomacromolecules. CMP‐Neu5Ac synthetase from Neisseria meningitidis (NmCSS) and sialyltransferase from Pasteurella multocida (PmST1) are combined in a one‐pot reaction giving access to sequence‐defined sialylated macromolecules. Surprisingly, when employing Tris(hydroxymethyl)aminomethane (Tris) as a buffer, formation of significant amounts of α‐linked Tris‐sialoside is observed as a side reaction. Further exploring and exploiting this unusual sialylation reaction, different neoglycosidic structures are synthesized showing that PmST1 can be used to derive both, sialylation on natural carbohydrates as well as on synthetic hydroxylated scaffolds. The combination of solid phase polymer synthesis and enzymatic sialyation is used to yield multivalent stereoselective 3′‐sialyllactose‐presenting macromolecules. The one pot reaction using synthetase NmCSS and sialyltransferase PmST1 is suitable to transfer sialic acid to either glycan acceptors, such as lactose, but as shown now in this study also to various nonglycan acceptors that contain a tris (hydroxy) motif.
ISSN:1616-5187
1616-5195
DOI:10.1002/mabi.202200358