Metabolic Oligosaccharide Engineering with Alkyne Sialic Acids Confers Neuraminidase Resistance and Inhibits Influenza Reproduction

Torben Heise; Christian Büll; Daniëlle M Beurskens; Emiel Rossing; Marien I de Jonge; Gosse J Adema; Thomas J Boltje; Jeroen D Langereis

doi:10.1021/acs.bioconjchem.7b00224

Metabolic Oligosaccharide Engineering with Alkyne Sialic Acids Confers Neuraminidase Resistance and Inhibits Influenza Reproduction

Torben Heise, Christian Büll, Daniëlle M Beurskens, Emiel Rossing, Marien I de Jonge, Gosse J Adema, Thomas J Boltje, Jeroen D Langereis

8 Citationer (Scopus)

Abstract

Metabolic incorporation of azide- or alkyne-modified sialic acids into the cellular glycosylation pathway enables the study of sialoglycan expression, localization, and trafficking via bioorthogonal chemistry. Herein, we report that such modifications of the sialic acid sugar can have a profound influence on their hydrolysis by neuraminidases (sialidase). Azidoacetyl (Az)-modified sialic acids were prone to neuraminidase cleavage, whereas propargyloxycarbonyl (Poc)-modified sialic acids were largely resistant to cleavage. Because the influenza virus infection cycle depends on the hydrolysis of host-cell-surface sialic acids, influenza cell-to-cell transmission was strongly reduced in Poc sialic acid glycoengineered host cells. The use of Poc sialic acids may disturb biological processes involving neuraminidase cleavage but also provides perspective for use in applications in which sialic acid hydrolysis is not desired, such as antibody modification, viral infection, etc.

Originalsprog	Engelsk
Tidsskrift	Bioconjugate Chemistry
Vol/bind	28
Udgave nummer	7
Sider (fra-til)	1811-1815
Antal sider	5
ISSN	1043-1802
DOI	https://doi.org/10.1021/acs.bioconjchem.7b00224
Status	Udgivet - 19 jul. 2017
Udgivet eksternt	Ja

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10.1021/acs.bioconjchem.7b00224Licens: CC BY-NC-ND

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title = "Metabolic Oligosaccharide Engineering with Alkyne Sialic Acids Confers Neuraminidase Resistance and Inhibits Influenza Reproduction",

abstract = "Metabolic incorporation of azide- or alkyne-modified sialic acids into the cellular glycosylation pathway enables the study of sialoglycan expression, localization, and trafficking via bioorthogonal chemistry. Herein, we report that such modifications of the sialic acid sugar can have a profound influence on their hydrolysis by neuraminidases (sialidase). Azidoacetyl (Az)-modified sialic acids were prone to neuraminidase cleavage, whereas propargyloxycarbonyl (Poc)-modified sialic acids were largely resistant to cleavage. Because the influenza virus infection cycle depends on the hydrolysis of host-cell-surface sialic acids, influenza cell-to-cell transmission was strongly reduced in Poc sialic acid glycoengineered host cells. The use of Poc sialic acids may disturb biological processes involving neuraminidase cleavage but also provides perspective for use in applications in which sialic acid hydrolysis is not desired, such as antibody modification, viral infection, etc.",

keywords = "Alkynes/chemistry, Humans, Hydrolysis, Metabolic Engineering/methods, Neuraminidase/metabolism, Oligosaccharides/chemistry, Orthomyxoviridae/physiology, Sialic Acids/chemistry, Virus Replication/drug effects",

author = "Torben Heise and Christian B{\"u}ll and Beurskens, {Dani{\"e}lle M} and Emiel Rossing and {de Jonge}, {Marien I} and Adema, {Gosse J} and Boltje, {Thomas J} and Langereis, {Jeroen D}",

year = "2017",

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doi = "10.1021/acs.bioconjchem.7b00224",

language = "English",

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T1 - Metabolic Oligosaccharide Engineering with Alkyne Sialic Acids Confers Neuraminidase Resistance and Inhibits Influenza Reproduction

AU - Heise, Torben

AU - Büll, Christian

AU - Beurskens, Daniëlle M

AU - Rossing, Emiel

AU - de Jonge, Marien I

AU - Adema, Gosse J

AU - Boltje, Thomas J

AU - Langereis, Jeroen D

PY - 2017/7/19

Y1 - 2017/7/19

N2 - Metabolic incorporation of azide- or alkyne-modified sialic acids into the cellular glycosylation pathway enables the study of sialoglycan expression, localization, and trafficking via bioorthogonal chemistry. Herein, we report that such modifications of the sialic acid sugar can have a profound influence on their hydrolysis by neuraminidases (sialidase). Azidoacetyl (Az)-modified sialic acids were prone to neuraminidase cleavage, whereas propargyloxycarbonyl (Poc)-modified sialic acids were largely resistant to cleavage. Because the influenza virus infection cycle depends on the hydrolysis of host-cell-surface sialic acids, influenza cell-to-cell transmission was strongly reduced in Poc sialic acid glycoengineered host cells. The use of Poc sialic acids may disturb biological processes involving neuraminidase cleavage but also provides perspective for use in applications in which sialic acid hydrolysis is not desired, such as antibody modification, viral infection, etc.

AB - Metabolic incorporation of azide- or alkyne-modified sialic acids into the cellular glycosylation pathway enables the study of sialoglycan expression, localization, and trafficking via bioorthogonal chemistry. Herein, we report that such modifications of the sialic acid sugar can have a profound influence on their hydrolysis by neuraminidases (sialidase). Azidoacetyl (Az)-modified sialic acids were prone to neuraminidase cleavage, whereas propargyloxycarbonyl (Poc)-modified sialic acids were largely resistant to cleavage. Because the influenza virus infection cycle depends on the hydrolysis of host-cell-surface sialic acids, influenza cell-to-cell transmission was strongly reduced in Poc sialic acid glycoengineered host cells. The use of Poc sialic acids may disturb biological processes involving neuraminidase cleavage but also provides perspective for use in applications in which sialic acid hydrolysis is not desired, such as antibody modification, viral infection, etc.

KW - Alkynes/chemistry

KW - Humans

KW - Hydrolysis

KW - Metabolic Engineering/methods

KW - Neuraminidase/metabolism

KW - Oligosaccharides/chemistry

KW - Orthomyxoviridae/physiology

KW - Sialic Acids/chemistry

KW - Virus Replication/drug effects

U2 - 10.1021/acs.bioconjchem.7b00224

DO - 10.1021/acs.bioconjchem.7b00224

M3 - Journal article

C2 - 28635265

SN - 1043-1802

VL - 28

SP - 1811

EP - 1815

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

IS - 7

ER -

Metabolic Oligosaccharide Engineering with Alkyne Sialic Acids Confers Neuraminidase Resistance and Inhibits Influenza Reproduction

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