title: Understanding viral neuraminidase inhibition by substituted difluorosialic acids.
abstract: Mechanism-based inhibition of influenza neuraminidases by difluorosialic acids (DFSA) is not only rendered highly specific by incorporation of 4-amino or 4-guanidine substituents but also the half-life for reactivation is greatly increased. Measurement of rate constants for spontaneous hydrolysis of a series of such substituted DFSAs reveals, surprisingly, that inherent inductive effects play very little role in this rate reduction and that interactions with the enzyme are more important.
authors.affiliation: Departments of Chemistry and Biochemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada. withers@chem.ubc.ca.
authors.forename: S
authors.initials: S
authors.lastname: Weck
authors.forename: K
authors.initials: K
authors.lastname: Robinson
authors.forename: M R
authors.initials: MR
authors.lastname: Smith
authors.forename: S G
authors.initials: SG
authors.lastname: Withers
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000201:enzymology*; D012794:Sialic Acids / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D012794:Sialic Acids; D009439:Neuraminidase