Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 17, Issue 15, Pages 5451-5464Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2009.06.036
Keywords
Thioglycosides; Sialic acid; Glycodendrimers; Sialidase inhibitors; Influenza virus
Funding
- Grants-in-Aid for Scientific Research [21550152] Funding Source: KAKEN
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In order to develop novel influenza sialidase inhibitors, we constructed a library of glycoclusters composed of twelve types of sialylated dendrimers with thioglycosidic linkage that are resistant to hydrolysis by the sialidases. These sialodendrimers were synthesized by condensation reaction between a thiosialoside modified on the aglycon terminal end by a thioacetyl group and twelve types of carbosilane dendrimers having brominated terminal ends under deacetylation conditions, and temporal re-protection was performed for purification. Removal of all protection of the glycodendrimers was accomplished by transesterification and subsequent saponification to provide corresponding water-soluble glycodendrimers in good yields. For investigation of the structure-activity relationship, dendrimer scaffolds having differences in number of the sugar moieties, such as 3-, 4-, 6-and 12-functionalized dendrimers, and in linkage patterns, such as normal aliphatic linkage, ether-and amide-linkages. Biological evaluations of these glycodendrimers showed that all of the ether-and amide-elongated compounds had inhibitory potencies for the influenza sialidases in the mM range, while compounds having normal aliphatic linkage did not have any activities except for a 12-functionalized compound. (C) 2009 Elsevier Ltd. All rights reserved.
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