title: Exploring the interactions of unsaturated glucuronides with influenza virus sialidase.
abstract: A series of C3 O-functionalized 2-acetamido-2-deoxy-Δ⁴-β-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-μM level; the introduction of small alkyl substituents or an acetyl group at C3 is also tolerated.
authors.affiliation: Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland 4222, Australia.
authors.forename: Beenu
authors.initials: B
authors.lastname: Bhatt
authors.forename: Raphael
authors.initials: R
authors.lastname: Böhm
authors.forename: Philip S
authors.initials: PS
authors.lastname: Kerry
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Dyason
authors.forename: Rupert J M
authors.initials: RJ
authors.lastname: Russell
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Thomson
authors.forename: Mark
authors.initials: M
authors.lastname: von Itzstein
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D020134:Catalytic Domain; D057075:Enzyme Assays; D005470:Fluorometry; D020719:Glucuronides / Q000138:chemical synthesis / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D009975:Orthomyxoviridae / Q000201:enzymology*; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000998:Antiviral Agents; D020719:Glucuronides; D009439:Neuraminidase