tetano
Editor, Senior Moderator
European J Org Chem. 2009 Jun;2009(16). doi: 10.1002/ejoc.200900117.
Synthesis and Biological Evaluation of Non-Hydrolizable 1,2,3-Triazole Linked Sialic Acid Derivatives as Neuraminidase Inhibitors.
We?wer M, Chen CC, Kemp MM, Linhardt RJ.
Source
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, 110, 8th Street, Troy, NY 12180 (USA).
Abstract
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.
KEYWORDS:
Cycloaddition, Influenza virus, N-glycosides, Neuraminidase inhibitors, Sialic acids
PMID:
24223493
[PubMed]
PMCID:
PMC3818918
Free PMC Article
http://www.ncbi.nlm.nih.gov/pubmed/24223493
Synthesis and Biological Evaluation of Non-Hydrolizable 1,2,3-Triazole Linked Sialic Acid Derivatives as Neuraminidase Inhibitors.
We?wer M, Chen CC, Kemp MM, Linhardt RJ.
Source
Department of Chemistry and Chemical Biology, Rensselaer Polytechnic Institute, 110, 8th Street, Troy, NY 12180 (USA).
Abstract
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.
KEYWORDS:
Cycloaddition, Influenza virus, N-glycosides, Neuraminidase inhibitors, Sialic acids
PMID:
24223493
[PubMed]
PMCID:
PMC3818918
Free PMC Article
http://www.ncbi.nlm.nih.gov/pubmed/24223493