Chemoenzymatic Syntheses of Sialylated Oligosaccharides Containing C5‐Modified Neuraminic Acids for Dual Inhibition of Hemagglutinins and Neuraminidases. Issue 30 (18th June 2015)

• Record Type: Journal Article
• Authors: Birikaki, Lémonia; Pradeau, Stéphanie; Armand, Sylvie; Priem, Bernard; Márquez‐Domínguez, Luis; Reyes‐Leyva, Julio; Santos‐López, Gerardo; Samain, Eric; Driguez, Hugues; Fort, Sébastien
• Is Part Of: Chemistry. Volume 21:Issue 30(2015)
• Page Start: 10903
• Page End: 10912
• Publication Date: 2015-06-18
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201500708
• Languages: English
• ISSNs: 0947-6539

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>A fast chemoenzymatic synthesis of sialylated oligosaccharides containing C5‐modified neuraminic acids is reported. Analogues of GM₃ and GM₂ ganglioside saccharidic portions where the acetyl group of Neu<italic>N</italic>Ac has been replaced by a phenylacetyl (PhAc) or a propanoyl (Prop) moiety have been efficiently prepared with metabolically engineered <italic>E. coli</italic> bacteria. GM₃ analogues were either obtained by chemoselective modification of biosynthetic <italic>N</italic>‐acetyl‐sialyllactoside (GM₃<italic>N</italic>Ac) or by direct bacterial synthesis using C5‐modified neuraminic acid precursors. The latter strategy proved to be very versatile as it led to an efficient synthesis of GM₂ analogues. These glycomimetics were assessed against hemagglutinins and sialidases. In particular, the GM₃<italic>N</italic>PhAc displayed a binding affinity for <italic>Maackia amurensis</italic> agglutinin (MAA) similar to that of GM₃<italic>N</italic>Ac, while being resistant to hydrolysis by <italic>Vibrio cholerae</italic> (<italic>VC</italic>) neuraminidase. A preliminary study with influenza viruses also confirmed a selective inhibition of N1 neuraminidase by GM₃<italic>N</italic>PhAc, suggesting potential developments for the detection of flu viruses and for fighting them.</p> </abstract>