Exploring the Interactions of Unsaturated Glucuronides with Influenza Virus Sialidase

Beenu Bhatt, Raphael Boehm, Philip S. Kerry, Jeffrey C. Dyason, Rupert J. M. Russell, Robin J. Thomson, Mark von Itzstein*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

A series of C3 O-functionalized 2-acetamido-2-deoxy-Delta(4)-beta-D-glucuronides were synthesized to explore noncharge interactions in subsite 2 of the influenza virus sialidase active site. In complex with A/N8 sialidase, the parent compound (C3 OH) inverts its solution conformation to bind with all substituents well positioned in the active site. The parent compound inhibits influenza virus sialidase at a sub-mu M level; the introduction of small alkyl substituents or an acetyl group at C3 is also tolerated.

Original languageEnglish
Pages (from-to)8963-8968
Number of pages6
JournalJournal of Medicinal Chemistry
Volume55
Issue number20
DOIs
Publication statusPublished - 25 Oct 2012

Keywords

  • NEURAMINIDASE INHIBITORS
  • BIOLOGICAL EVALUATION
  • ACID-DERIVATIVES
  • OSELTAMIVIR
  • ZANAMIVIR
  • DESIGN
  • DISCOVERY
  • A-315675
  • ANALOGS
  • BINDING

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