Biological Properties of N-Acyl and N-Haloacetyl Neuraminic Acids: Processing by Enzymes of Sialic Acid Metabolism, and Interaction with Influenza Virus

• Published in: Bioorganic & medicinal chemistry Vol. 10; no. 10; pp. 3175 - 3185
• Main Authors: Humphrey, Andrew J, Fremann, Claire, Critchley, Peter, Malykh, Yanina, Schauer, Roland, Bugg, Timothy D.H
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.10.2002; Elsevier Science
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Escherichia coli - enzymology; Glycolipids - metabolism; Influenza A virus - drug effects; Influenza A virus - enzymology; Influenza A virus - metabolism; Medical sciences; Mixed Function Oxygenases - metabolism; N-Acylneuraminate Cytidylyltransferase - metabolism; Neuraminic Acids - chemistry; Neuraminic Acids - metabolism; Neuraminic Acids - pharmacology; Neuraminidase - antagonists & inhibitors; Oxo-Acid-Lyases - metabolism; Pharmacology. Drug treatments; Sialic Acids - chemistry; Sialic Acids - metabolism; Sialic Acids - pharmacology; Structure-Activity Relationship; Substrate Specificity; Surface Plasmon Resonance; Swine; Sialic acid; Orthomyxoviridae; Esterases; Lyases; Phosphoric diester hydrolases; Oxo-acid-lyases; Ketoaldonic acid; Enzymatic activity; Structure activity relation; Antiviral; CMP-N-acylneuraminate phosphodiesterase; Halogen Organic compounds; Enzyme; Enzyme inhibitor; N-Acetylneuraminate lyase; In vitro; Virus; Carbon-carbon lyases; Influenzavirus A; Influenza A virus; Glycosidases; Aminoglycoside; Exo-α-sialidase; Neuraminic acid; Hydrolases; Carboxamide; O-Glycosidases; Enzymatic reaction
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(02)00213-4

Graphic 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.