title: GS4071 is a slow-binding inhibitor of influenza neuraminidase from both A and B strains.
abstract: The kinetics of inhibition of purified influenza neuraminidases from A/Tokyo/3/67 and B/Memphis/3/89 influenza viruses by (3R,4R,5S)-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene- 1-carboxylic acid (GS4071) were investigated. Progress curve experiments established that GS4071 is a time dependent inhibitor of both A and B strains of influenza neuraminidase. The apparent association and dissociation rate constants, as well as the overall Ki values, were only modestly different for the two neuraminidase strains. The time dependent inhibition phenomenon, often referred to as slow-binding inhibition, appears to be a consequence of the very slow rate of dissociation of the compound from influenza neuraminidase.
authors.affiliation: Infectious Diseases Research, Abbott Laboratories, Illinois 60064, USA. warren.kati@abbott.com
authors.forename: W M
authors.initials: WM
authors.lastname: Kati
authors.forename: A S
authors.initials: AS
authors.lastname: Saldivar
authors.forename: F
authors.initials: F
authors.lastname: Mohamadi
authors.forename: H L
authors.initials: HL
authors.lastname: Sham
authors.forename: W G
authors.initials: WG
authors.lastname: Laver
authors.forename: W E
authors.initials: WE
authors.lastname: Kohlbrenner
mesh_terms: D000081:Acetamides / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006860:Hydrogen Bonding; D009980:Influenza A virus / Q000187:drug effects* / Q000201:enzymology*; D009981:Influenza B virus / Q000187:drug effects* / Q000201:enzymology*; D007700:Kinetics; D009439:Neuraminidase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D053139:Oseltamivir; D011487:Protein Conformation; D013045:Species Specificity; D014867:Water
chemical_list: D000081:Acetamides; D004791:Enzyme Inhibitors; D014867:Water; D053139:Oseltamivir; D009439:Neuraminidase