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

Patrick B. Konietzny; Hannelore Peters; Marc L. Hofer; Ulla I.M. Gerling-Driessen; Robert P. de Vries; Thomas Peters; Laura Hartmann

doi:10.1002/mabi.202200358

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

Patrick B. Konietzny, Hannelore Peters, Marc L. Hofer, Ulla I.M. Gerling-Driessen, Robert P. de Vries, Thomas Peters^*, Laura Hartmann^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	2200358
Journal	Macromolecular Bioscience
Volume	22
Issue number	12
DOIs	https://doi.org/10.1002/mabi.202200358
Publication status	Published - Dec 2022

Bibliographical note

Funding Information:
P.B.K. and H.P. contributed equally to this work. L.H. is corresponding author for synthetic chemistry and enzymatic reactions leading to the aglycon scaffolds, T.P. for enzymatic chemistry and in‐line NMR analysis. The authors thank the German Research Foundation for support through the research group “VIROCARB” (FOR 2327, P6/P7). The authors also thank Robert Creutznacher and Thorsten Biet for assistance with NMR experiments.

Publisher Copyright:
© 2022 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.

Funding

P.B.K. and H.P. contributed equally to this work. L.H. is corresponding author for synthetic chemistry and enzymatic reactions leading to the aglycon scaffolds, T.P. for enzymatic chemistry and in‐line NMR analysis. The authors thank the German Research Foundation for support through the research group “VIROCARB” (FOR 2327, P6/P7). The authors also thank Robert Creutznacher and Thorsten Biet for assistance with NMR experiments.

Keywords

chemoenzymatic synthesis
glycomacromolecules
neoglycoside
sialic acid
solid phase polymer synthesis

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Macromolecular Bioscience - 2022 - Konietzny - Enzymatic Sialylation of Synthetic Multivalent Scaffolds From 3Final published version, 1.76 MBLicence: CC BY

Cite this

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title = "Enzymatic Sialylation of Synthetic Multivalent Scaffolds: From 3′-Sialyllactose Glycomacromolecules to Novel Neoglycosides",

abstract = "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.",

keywords = "chemoenzymatic synthesis, glycomacromolecules, neoglycoside, sialic acid, solid phase polymer synthesis",

author = "Konietzny, \{Patrick B.\} and Hannelore Peters and Hofer, \{Marc L.\} and Gerling-Driessen, \{Ulla I.M.\} and \{de Vries\}, \{Robert P.\} and Thomas Peters and Laura Hartmann",

note = "Funding Information: P.B.K. and H.P. contributed equally to this work. L.H. is corresponding author for synthetic chemistry and enzymatic reactions leading to the aglycon scaffolds, T.P. for enzymatic chemistry and in‐line NMR analysis. The authors thank the German Research Foundation for support through the research group “VIROCARB” (FOR 2327, P6/P7). The authors also thank Robert Creutznacher and Thorsten Biet for assistance with NMR experiments. Publisher Copyright: {\textcopyright} 2022 The Authors. Macromolecular Bioscience published by Wiley-VCH GmbH.",

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AU - de Vries, Robert P.

AU - Peters, Thomas

AU - Hartmann, Laura

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N2 - 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.

AB - 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.

KW - chemoenzymatic synthesis

KW - glycomacromolecules

KW - neoglycoside

KW - sialic acid

KW - solid phase polymer synthesis

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ER -

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

Abstract

Bibliographical note

Funding

Keywords

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