Sialic Acid Glycoengineering Using an Unnatural Sialic Acid for the Detection of Sialoglycan Biosynthesis Defects and On-Cell Synthesis of Siglec Ligands

Christian Büll; Torben Heise; Daniëlle M H Beurskens; Moniek Riemersma; Angel Ashikov; Floris P J T Rutjes; Toin H van Kuppevelt; Dirk J Lefeber; Martijn H den Brok; Gosse J Adema; Thomas J Boltje

doi:10.1021/acschembio.5b00501

Sialic Acid Glycoengineering Using an Unnatural Sialic Acid for the Detection of Sialoglycan Biosynthesis Defects and On-Cell Synthesis of Siglec Ligands

Christian Büll, Torben Heise, Daniëlle M H Beurskens, Moniek Riemersma, Angel Ashikov, Floris P J T Rutjes, Toin H van Kuppevelt, Dirk J Lefeber, Martijn H den Brok, Gosse J Adema, Thomas J Boltje

20 Citations (Scopus)

Abstract

Sialoglycans play a vital role in physiology, and aberrant sialoglycan expression is associated with a broad spectrum of diseases. Since biosynthesis of sialoglycans is only partially regulated at the genetic level, chemical tools are crucial to study their function. Here, we report the development of propargyloxycarbonyl sialic acid (Ac5NeuNPoc) as a powerful tool for sialic acid glycoengineering. Ac5NeuNPoc showed strongly increased labeling efficiency and exhibited less toxicity compared to those of widely used mannosamine analogues in vitro and was also more efficiently incorporated into sialoglycans in vivo. Unlike mannosamine analogues, Ac5NeuNPoc was exclusively utilized in the sialoglycan biosynthesis pathway, allowing a genetic defect in sialic acid biosynthesis to be specifically detected. Furthermore, Ac5NeuNPoc-based sialic acid glycoengineering enabled the on-cell synthesis of high-affinity Siglec-7 ligands and the identification of a novel Siglec-2 ligand. Thus, Ac5NeuNPoc glycoengineering is a highly efficient, nontoxic, and selective approach to study and modulate sialoglycan interactions on living cells.

Original language	English
Journal	ACS chemical biology
Volume	10
Issue number	10
Pages (from-to)	2353-63
Number of pages	11
ISSN	1554-8929
DOIs	https://doi.org/10.1021/acschembio.5b00501
Publication status	Published - 16 Oct 2015
Externally published	Yes

Keywords

Animals
Blotting, Western
Carbohydrate Sequence
Female
Flow Cytometry
Glycoproteins/chemistry
Humans
Jurkat Cells
Ligands
Membrane Glycoproteins/chemistry
Mice
Microscopy, Confocal
N-Acetylneuraminic Acid/chemistry
Polysaccharides/chemistry
Protein Binding
Protein Engineering
Sialic Acid Binding Immunoglobulin-like Lectins/chemistry

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10.1021/acschembio.5b00501

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Büll, C., Heise, T., Beurskens, D. M. H., Riemersma, M., Ashikov, A., Rutjes, F. P. J. T., van Kuppevelt, T. H., Lefeber, D. J., den Brok, M. H., Adema, G. J., & Boltje, T. J. (2015). Sialic Acid Glycoengineering Using an Unnatural Sialic Acid for the Detection of Sialoglycan Biosynthesis Defects and On-Cell Synthesis of Siglec Ligands. ACS chemical biology, 10(10), 2353-63. https://doi.org/10.1021/acschembio.5b00501

Sialic Acid Glycoengineering Using an Unnatural Sialic Acid for the Detection of Sialoglycan Biosynthesis Defects and On-Cell Synthesis of Siglec Ligands. / Büll, Christian; Heise, Torben; Beurskens, Daniëlle M H et al.
In: ACS chemical biology, Vol. 10, No. 10, 16.10.2015, p. 2353-63.

Research output: Contribution to journal › Journal article › Research › peer-review

Büll, C, Heise, T, Beurskens, DMH, Riemersma, M, Ashikov, A, Rutjes, FPJT, van Kuppevelt, TH, Lefeber, DJ, den Brok, MH, Adema, GJ & Boltje, TJ 2015, 'Sialic Acid Glycoengineering Using an Unnatural Sialic Acid for the Detection of Sialoglycan Biosynthesis Defects and On-Cell Synthesis of Siglec Ligands', ACS chemical biology, vol. 10, no. 10, pp. 2353-63. https://doi.org/10.1021/acschembio.5b00501

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abstract = "Sialoglycans play a vital role in physiology, and aberrant sialoglycan expression is associated with a broad spectrum of diseases. Since biosynthesis of sialoglycans is only partially regulated at the genetic level, chemical tools are crucial to study their function. Here, we report the development of propargyloxycarbonyl sialic acid (Ac5NeuNPoc) as a powerful tool for sialic acid glycoengineering. Ac5NeuNPoc showed strongly increased labeling efficiency and exhibited less toxicity compared to those of widely used mannosamine analogues in vitro and was also more efficiently incorporated into sialoglycans in vivo. Unlike mannosamine analogues, Ac5NeuNPoc was exclusively utilized in the sialoglycan biosynthesis pathway, allowing a genetic defect in sialic acid biosynthesis to be specifically detected. Furthermore, Ac5NeuNPoc-based sialic acid glycoengineering enabled the on-cell synthesis of high-affinity Siglec-7 ligands and the identification of a novel Siglec-2 ligand. Thus, Ac5NeuNPoc glycoengineering is a highly efficient, nontoxic, and selective approach to study and modulate sialoglycan interactions on living cells. ",

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AU - Büll, Christian

AU - Heise, Torben

AU - Beurskens, Daniëlle M H

AU - Riemersma, Moniek

AU - Ashikov, Angel

AU - Rutjes, Floris P J T

AU - van Kuppevelt, Toin H

AU - Lefeber, Dirk J

AU - den Brok, Martijn H

AU - Adema, Gosse J

AU - Boltje, Thomas J

PY - 2015/10/16

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N2 - Sialoglycans play a vital role in physiology, and aberrant sialoglycan expression is associated with a broad spectrum of diseases. Since biosynthesis of sialoglycans is only partially regulated at the genetic level, chemical tools are crucial to study their function. Here, we report the development of propargyloxycarbonyl sialic acid (Ac5NeuNPoc) as a powerful tool for sialic acid glycoengineering. Ac5NeuNPoc showed strongly increased labeling efficiency and exhibited less toxicity compared to those of widely used mannosamine analogues in vitro and was also more efficiently incorporated into sialoglycans in vivo. Unlike mannosamine analogues, Ac5NeuNPoc was exclusively utilized in the sialoglycan biosynthesis pathway, allowing a genetic defect in sialic acid biosynthesis to be specifically detected. Furthermore, Ac5NeuNPoc-based sialic acid glycoengineering enabled the on-cell synthesis of high-affinity Siglec-7 ligands and the identification of a novel Siglec-2 ligand. Thus, Ac5NeuNPoc glycoengineering is a highly efficient, nontoxic, and selective approach to study and modulate sialoglycan interactions on living cells.

AB - Sialoglycans play a vital role in physiology, and aberrant sialoglycan expression is associated with a broad spectrum of diseases. Since biosynthesis of sialoglycans is only partially regulated at the genetic level, chemical tools are crucial to study their function. Here, we report the development of propargyloxycarbonyl sialic acid (Ac5NeuNPoc) as a powerful tool for sialic acid glycoengineering. Ac5NeuNPoc showed strongly increased labeling efficiency and exhibited less toxicity compared to those of widely used mannosamine analogues in vitro and was also more efficiently incorporated into sialoglycans in vivo. Unlike mannosamine analogues, Ac5NeuNPoc was exclusively utilized in the sialoglycan biosynthesis pathway, allowing a genetic defect in sialic acid biosynthesis to be specifically detected. Furthermore, Ac5NeuNPoc-based sialic acid glycoengineering enabled the on-cell synthesis of high-affinity Siglec-7 ligands and the identification of a novel Siglec-2 ligand. Thus, Ac5NeuNPoc glycoengineering is a highly efficient, nontoxic, and selective approach to study and modulate sialoglycan interactions on living cells.

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KW - Carbohydrate Sequence

KW - Female

KW - Flow Cytometry

KW - Glycoproteins/chemistry

KW - Humans

KW - Jurkat Cells

KW - Ligands

KW - Membrane Glycoproteins/chemistry

KW - Mice

KW - Microscopy, Confocal

KW - N-Acetylneuraminic Acid/chemistry

KW - Polysaccharides/chemistry

KW - Protein Binding

KW - Protein Engineering

KW - Sialic Acid Binding Immunoglobulin-like Lectins/chemistry

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DO - 10.1021/acschembio.5b00501

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SN - 1554-8929

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SP - 2353

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JO - ACS chemical biology

JF - ACS chemical biology

IS - 10

ER -

Sialic Acid Glycoengineering Using an Unnatural Sialic Acid for the Detection of Sialoglycan Biosynthesis Defects and On-Cell Synthesis of Siglec Ligands

Abstract

Keywords

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