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

Torben Heise, Christian Bull, Danielle M. Beurskens, Emiel Rossing, Marien I. de Jonge, Gosse J. Adema, Thomas J. Boltje*, Jeroen D. Langereis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

13 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)1811-1815
Number of pages5
JournalBioconjugate Chemistry
Volume28
Issue number7
DOIs
Publication statusPublished - Jul 2017

Keywords

  • ACYL SIDE-CHAIN
  • TERMINAL ALKYNES
  • VIRUS-INFECTION
  • PERSPECTIVE
  • CHEMISTRY
  • AZIDES

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