Chemoenzymatic Syntheses of Sialylated Oligosaccharides Containing C5-Modified Neuraminic Acids for Dual Inhibition of Hemagglutinins and Neuraminidases
Por:
Birikaki L., Pradeau S., Armand S., Priem B., Márquez-Domínguez L., Reyes-Leyva J., Santos-Lõpez G., Samain E., Driguez H., Fort S.
Publicada:
1 ene 2015
Resumen:
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 Analogues of GM3 and GM2 ganglioside saccharidic portions where the acetyl group of NeuNAc has been replaced by a phenylacetyl (PhAc) or a propanoyl (Prop) moiety have been efficiently prepared with metabolically engineered E. coli bacteria. GM3 analogues were either obtained by chemoselective modification of biosynthetic N-acetyl-sialyllactoside (GM3NAc) 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 GM3NPhAc displayed a binding affinity for Maackia amurensis agglutinin (MAA) similar to that of GM3NAc, 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 GM3NPhAc, suggesting potential developments for the detection of flu viruses and for fighting them. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Filiaciones:
Birikaki L.:
Univ. Grenoble Alpes, CERMAV, Grenoble, 38000, France
CNRS, CERMAV, Grenoble, 38000, France
Pradeau S.:
Univ. Grenoble Alpes, CERMAV, Grenoble, 38000, France
CNRS, CERMAV, Grenoble, 38000, France
Armand S.:
Univ. Grenoble Alpes, CERMAV, Grenoble, 38000, France
CNRS, CERMAV, Grenoble, 38000, France
Priem B.:
Univ. Grenoble Alpes, CERMAV, Grenoble, 38000, France
CNRS, CERMAV, Grenoble, 38000, France
Márquez-Domínguez L.:
Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano Del Seguro Social, Metepec, Puebla, Mexico
Reyes-Leyva J.:
Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano Del Seguro Social, Metepec, Puebla, Mexico
Santos-Lõpez G.:
Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano Del Seguro Social, Metepec, Puebla, Mexico
Samain E.:
Univ. Grenoble Alpes, CERMAV, Grenoble, 38000, France
CNRS, CERMAV, Grenoble, 38000, France
Driguez H.:
Univ. Grenoble Alpes, CERMAV, Grenoble, 38000, France
CNRS, CERMAV, Grenoble, 38000, France
Fort S.:
Univ. Grenoble Alpes, CERMAV, Grenoble, 38000, France
CNRS, CERMAV, Grenoble, 38000, France
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