title: Structure-guided design of a novel class of benzyl-sulfonate inhibitors for influenza virus neuraminidase.
abstract: Influenza NA (neuraminidase) is an antiviral target of high pharmaceutical interest because of its essential role in cleaving sialic acid residues from cell surface glycoproteins and facilitating release of virions from infected cells. The present paper describes the use of structural information in the progressive design from a lead binding ion (a sulfate) to a potent submicromolor inhibitor (K(i) 0.13 microM). Structural information derived from the X-ray structure of an NA complexed with several sulfate ions, in combination with results derived from affinity labelling and molecular modelling studies, was used to guide design of potent sulfonic acid-based inhibitors. These inhibitors are structural fragments of the polysulfonate triazine dye Cibacron Blue 3GA and represent novel lead scaffolds for designing non-carbohydrate inhibitors for influenza neuraminidases.
authors.affiliation: Laboratory of Enzyme Technology, Department of Agricultural Biotechnology, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Platis
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Smith
authors.forename: Trevor
authors.initials: T
authors.lastname: Huyton
authors.forename: Nikolaos E
authors.initials: NE
authors.lastname: Labrou
mesh_terms: D000476:Alkanesulfonates / Q000737:chemistry*; D000595:Amino Acid Sequence; D001665:Binding Sites; D015195:Drug Design; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D009975:Orthomyxoviridae / Q000201:enzymology*; D019920:Photoaffinity Labels / Q000737:chemistry; D025941:Protein Interaction Mapping; D016415:Sequence Alignment; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry
chemical_list: D000476:Alkanesulfonates; D008024:Ligands; D019920:Photoaffinity Labels; D014227:Triazines; C012842:Cibacron Blue F 3GA; D009439:Neuraminidase