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Bioconjug Chem. 2017 Jun 21. doi: 10.1021/acs.bioconjchem.7b00224. [Epub ahead of print]
Metabolic Oligosaccharide Engineering with Alkyne Sialic Acids Confers Neuraminidase Resistance and Inhibits Influenza Reproduction.
Heise T, B?ll C, Beurskens DMH, Rossing E, de Jonge M, Adema GJ, Boltje TJ, Langereis J.
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 modified sialic acids were prone to neuraminidase cleavage, whereas propargyloxycarbonyl (Poc) modified sialic acids were largely resistent to cleavage. As the influenza virus infection cycle depends on hydrolysis of host cell surface sialic acids, influenza cell-to-cell transmission was strongly reduced in Poc sialic acid glycoengineerd host cells. The use of Poc sialic acids may disturb biological processes involving neuraminidase cleavage but also provides perspective for the use in applications in which sialic acid hydrolysis is undesired such as antibody modification, viral infection etc.
PMID: 28635265 DOI: 10.1021/acs.bioconjchem.7b00224
Metabolic Oligosaccharide Engineering with Alkyne Sialic Acids Confers Neuraminidase Resistance and Inhibits Influenza Reproduction.
Heise T, B?ll C, Beurskens DMH, Rossing E, de Jonge M, Adema GJ, Boltje TJ, Langereis J.
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 modified sialic acids were prone to neuraminidase cleavage, whereas propargyloxycarbonyl (Poc) modified sialic acids were largely resistent to cleavage. As the influenza virus infection cycle depends on hydrolysis of host cell surface sialic acids, influenza cell-to-cell transmission was strongly reduced in Poc sialic acid glycoengineerd host cells. The use of Poc sialic acids may disturb biological processes involving neuraminidase cleavage but also provides perspective for the use in applications in which sialic acid hydrolysis is undesired such as antibody modification, viral infection etc.
PMID: 28635265 DOI: 10.1021/acs.bioconjchem.7b00224