tetano
Editor, Senior Moderator
Chemistry. 2015 Jun 18. doi: 10.1002/chem.201500708. [Epub ahead of print]
[h=1]Chemoenzymatic Syntheses of Sialylated Oligosaccharides Containing C5-Modified Neuraminic Acids for Dual Inhibition of Hemagglutinins and Neuraminidases.[/h] Birikaki L[SUP]1,[/SUP][SUP]2[/SUP], Pradeau S[SUP]1,[/SUP][SUP]2[/SUP], Armand S[SUP]1,[/SUP][SUP]2[/SUP], Priem B[SUP]1,[/SUP][SUP]2[/SUP], M?rquez-Dom?nguez L[SUP]3[/SUP], Reyes-Leyva J[SUP]3[/SUP], Santos-L?pez G[SUP]3[/SUP], Samain E[SUP]1,[/SUP][SUP]2[/SUP], Driguez H[SUP]1,[/SUP][SUP]2[/SUP], Fort S[SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A fast chemoenzymatic synthesis of sialylated oligosaccharides containing C5-modified neuraminic acids is reported. Analogues of GM[SUB]3[/SUB] and GM[SUB]2[/SUB] ganglioside saccharidic portions where the acetyl group of NeuNAc has been replaced by a phenylacetyl (PhAc) or a propanoyl (Prop) moiety have been efficiently prepared with metabolically engineered E. coli bacteria. GM[SUB]3[/SUB] analogues were either obtained by chemoselective modification of biosynthetic N-acetyl-sialyllactoside (GM[SUB]3[/SUB] NAc) 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[SUB]2[/SUB] analogues. These glycomimetics were assessed against hemagglutinins and sialidases. In particular, the GM[SUB]3[/SUB] NPhAc displayed a binding affinity for Maackia amurensis agglutinin (MAA) similar to that of GM[SUB]3[/SUB] NAc, 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[SUB]3[/SUB] NPhAc, suggesting potential developments for the detection of flu viruses and for fighting them.
? 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[h=4]KEYWORDS:[/h] chemoenzymatic synthesis; glycomimetics; influenza; neuraminic acids; oligosaccharides
PMID: 26088695 [PubMed - as supplied by publisher]
[h=1]Chemoenzymatic Syntheses of Sialylated Oligosaccharides Containing C5-Modified Neuraminic Acids for Dual Inhibition of Hemagglutinins and Neuraminidases.[/h] Birikaki L[SUP]1,[/SUP][SUP]2[/SUP], Pradeau S[SUP]1,[/SUP][SUP]2[/SUP], Armand S[SUP]1,[/SUP][SUP]2[/SUP], Priem B[SUP]1,[/SUP][SUP]2[/SUP], M?rquez-Dom?nguez L[SUP]3[/SUP], Reyes-Leyva J[SUP]3[/SUP], Santos-L?pez G[SUP]3[/SUP], Samain E[SUP]1,[/SUP][SUP]2[/SUP], Driguez H[SUP]1,[/SUP][SUP]2[/SUP], Fort S[SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] A fast chemoenzymatic synthesis of sialylated oligosaccharides containing C5-modified neuraminic acids is reported. Analogues of GM[SUB]3[/SUB] and GM[SUB]2[/SUB] 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. GM[SUB]3[/SUB] analogues were either obtained by chemoselective modification of biosynthetic N-acetyl-sialyllactoside (GM[SUB]3[/SUB] NAc) 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[SUB]2[/SUB] analogues. These glycomimetics were assessed against hemagglutinins and sialidases. In particular, the GM[SUB]3[/SUB] NPhAc displayed a binding affinity for Maackia amurensis agglutinin (MAA) similar to that of GM[SUB]3[/SUB] NAc, 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[SUB]3[/SUB] NPhAc, suggesting potential developments for the detection of flu viruses and for fighting them.
? 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
[h=4]KEYWORDS:[/h] chemoenzymatic synthesis; glycomimetics; influenza; neuraminic acids; oligosaccharides
PMID: 26088695 [PubMed - as supplied by publisher]