title: Synthesis and evaluation of C-9 modified N-acetylneuraminic acid derivatives as substrates for N-acetylneuraminic acid aldolase.
abstract: Several C-9 modified N-acetylneuraminic acid derivatives have been synthesised and evaluated as substrates of N-acetylneuraminic acid aldolase. Simple C-9 acyl or ether modified derivatives of N-acetylneuraminic acid were found to be accepted as substrates by the enzyme, albeit being transformed more slowly than Neu5Ac itself. 1H NMR spectroscopy was used to evaluate the extent of the enzyme catalysed transformation of these compounds. Interestingly, the chain-extended Neu5Ac derivative 16 is not a substrate for N-acetylneuraminate lyase and behaves as an inhibitor of the enzyme.
authors.affiliation: Department of Medicinal Chemistry, Monash University, Parkville, Victoria, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kiefelt
authors.forename: J C
authors.initials: JC
authors.lastname: Wilson
authors.forename: S
authors.initials: S
authors.lastname: Bennett
authors.forename: M
authors.initials: M
authors.lastname: Gredley
authors.forename: M
authors.initials: M
authors.lastname: von Itzstein
mesh_terms: D001426:Bacterial Proteins; D001665:Binding Sites; D004926:Escherichia coli / Q000201:enzymology; D007700:Kinetics; D008567:Membranes, Artificial; D015335:Molecular Probes; D019158:N-Acetylneuraminic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry*; D007652:Oxo-Acid-Lyases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D008567:Membranes, Artificial; D015335:Molecular Probes; D007652:Oxo-Acid-Lyases; C018728:N-acetylneuraminate lyase; D019158:N-Acetylneuraminic Acid