Unsaturated N-acetyl- D-glucosaminuronic acid glycosides as inhibitors of influenza virus sialidase

Glycoconj J. 2006 Feb;23(1-2):127-33. doi: 10.1007/s10719-006-5445-9.

Abstract

The threat of pandemic influenza is a significant concern of governments worldwide. There is a very limited and relatively expensive armament to tackle such a pandemic should it occur. This fact provides much impetus to the scientific community for the discovery of new and less expensive anti-influenza drugs. Our longstanding interest in the inhibition of influenza virus sialidase, coupled with the development of simple carbohydrates that mimic an unsaturated derivative of the enzyme's naturally-occurring ligand, N-acetylneuraminic acid, has led us to investigate the development of influenza virus sialidase inhibitors based on these mimetics. We have successfully prepared a range of these compounds, in good yield, from the relatively inexpensive carbohydrate N-acetylglucosamine utilising a short synthetic procedure. We have employed a sialidase inhibition assay for biological evaluation of the target compounds and to our delight these mimetics have displayed significant inhibition of influenza virus sialidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Glycosides / chemistry*
  • Models, Molecular
  • Molecular Mimicry
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / chemistry
  • Protein Conformation
  • Uronic Acids / chemistry*

Substances

  • Enzyme Inhibitors
  • Glycosides
  • Uronic Acids
  • N-acetylglucosaminuronic acid
  • Neuraminidase