Biological properties of N-acyl and N-haloacetyl neuraminic acids: processing by enzymes of sialic acid metabolism, and interaction with influenza virus.
Several unnatural N-acyl neuraminic acids (N-propionyl, N-hexanoyl, N-benzoyl, N-trifluoroacetyl, N-chloroacetyl, N-difluoroacetyl) were prepared enzymatically using immobilised sialic acid aldolase. N-Trifluoroacetyl-, N-chloroacetyl- and N-difluoroacetyl neuraminic acids were shown to enhance up to 10-fold the rate of association of influenza virus A to a sialoglycolipid neomembrane by surface plasmon resonance, and were found to act as weak inhibitors (K(iapp) 0.45-2.0 mM) of influenza virus neuraminidase. The N-propionyl, N-chloroacetyl- and N-difluoroacetyl neuraminic acids were found to be substrates for recombinant Escherichia coli CMP sialate synthase, to give the corresponding CMP-N-acyl-neuraminic acids. CMP-N-propionyl neuraminic acid was found not to be a substrate for CMP-N-acetyl neuraminic acid hydroxylase from pig submandibular gland.
Humphrey
Andrew J
AJ
Department of Chemistry, University of Southampton, Highfield, Southampton, UK.
Fremann
Claire
C
Critchley
Peter
P
Malykh
Yanina
Y
Schauer
Roland
R
Bugg
Timothy D H
TD
D000818:Animals; D004926:Escherichia coli / Q000201:enzymology; D006017:Glycolipids / Q000378:metabolism; D009980:Influenza A virus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D000216:N-Acylneuraminate Cytidylyltransferase / Q000378:metabolism; D009438:Neuraminic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D007652:Oxo-Acid-Lyases / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D020349:Surface Plasmon Resonance; D013552:Swine
D006017:Glycolipids; D009438:Neuraminic Acids; D012794:Sialic Acids; D006899:Mixed Function Oxygenases; C074383:CMPacetylneuraminate monooxygenase; D000216:N-Acylneuraminate Cytidylyltransferase; D009439:Neuraminidase; D007652:Oxo-Acid-Lyases; C018728:N-acetylneuraminate lyase