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Chemoenzymatic Syntheses of Sialylated Oligosaccharides Containing C5‐Modified Neuraminic Acids for Dual Inhibition of Hemagglutinins and Neuraminidases
Author(s) -
Birikaki Lémonia,
Pradeau Stéphanie,
Armand Sylvie,
Priem Bernard,
MárquezDomínguez Luis,
ReyesLeyva Julio,
SantosLópez Gerardo,
Samain Eric,
Driguez Hugues,
Fort Sébastien
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201500708
Subject(s) - neuraminic acid , neuraminidase , sialidase , chemistry , biochemistry , enzyme , vibrio cholerae , moiety , sialic acid , bacteria , stereochemistry , biology , genetics
A fast chemoenzymatic synthesis of sialylated oligosaccharides containing C5‐modified neuraminic acids is reported. Analogues of GM 3 and GM 2 ganglioside saccharidic portions where the acetyl group of Neu N Ac has been replaced by a phenylacetyl (PhAc) or a propanoyl (Prop) moiety have been efficiently prepared with metabolically engineered E. coli bacteria. GM 3 analogues were either obtained by chemoselective modification of biosynthetic N ‐acetyl‐sialyllactoside (GM 3 N 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 GM 2 analogues. These glycomimetics were assessed against hemagglutinins and sialidases. In particular, the GM 3 N PhAc displayed a binding affinity for Maackia amurensis agglutinin (MAA) similar to that of GM 3 N Ac, while being resistant to hydrolysis by Vibrio cholerae ( VC ) neuraminidase. A preliminary study with influenza viruses also confirmed a selective inhibition of N1 neuraminidase by GM 3 N PhAc, suggesting potential developments for the detection of flu viruses and for fighting them.