Synthesis and biological evaluation of 1,2,3-triazole linked sialic acid derivatives as neuraminidase inhibitors

Weïwer, M.
Chen, C.C.
Kemp, M.M.
Linhardt, Robert J.
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Synthesis and biological evaluation of 1,2,3-triazole linked sialic acid derivatives as neuraminidase inhibitors, M. Weïwer, C.-C. Chen, M. M. Kemp, R. J. Linhardt, European Journal of Organic Chemistry, 2611–2620, 2009.
α-Sialic acid azide 1 has been used as a substrate for the efficient preparation of 1,2,3-triazole derivatives of sialic acid using the copper-catalyzed azide-alkyne Huisgen cycloaddition ("click chemistry"). Our approach is to generate non-natural N-glycosides of sialic acid that are resistant to neuraminidase catalyzed hydrolysis as opposed to the natural O-glycosides. These N-glycosides would act as neuraminidase inhibitors to prevent the release of new virions. As a preliminary study, a small library of 1,2,3-triazole-linked sialic acid derivatives has been synthesized in 71-89% yield. A disaccharide mimic of sialic acid has also been prepared using the α-sialic acid azide 1 and a C-8 propargyl sialic acid acceptor in 68% yield. A model sialic acid coated dendrimer was also synthesized from a per-propargylated pentaerythritol acceptor. These novel sialic acid derivatives were then evaluated as potential neuraminidase inhibitors using a 96-well plate fluorescence assay; micromolar IC50 values were observed, comparable to the known sialidase inhibitor Neu5Ac2en.
European Journal of Organic Chemistry, 2611–2620
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The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
European Chemical Societies Publishing
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
European Journal of Organic Chemistry
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