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

[Image: see text] 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.