Abstract
We report the synthesis of a small series of 6"-triazol-1-yl-substituted α-GalCer analogues by late-stage conversion of the 6"-OH to an azide group, copper-catalyzed azide-alkyne cycloaddition and final deprotection. When evaluated for their capacity to induce IL-2 secretion in vitro, all compounds proved equally potent or superior to α-GalCer. The S.A.R suggests that the improved antigenic activity is mainly triggered by the triazole functionalization in se. While the introduction of selected substitutuents at C-4 of this heterocyclic ring is tolerated, this generally fails to further improve antigenicity.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / chemical synthesis
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Adjuvants, Immunologic / chemistry
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Adjuvants, Immunologic / pharmacology
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Animals
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Bone Marrow Cells / drug effects
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Bone Marrow Cells / immunology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Galactosylceramides / chemical synthesis*
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Galactosylceramides / chemistry
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Galactosylceramides / pharmacology*
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Ligands
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Mice
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Natural Killer T-Cells / drug effects*
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Natural Killer T-Cells / immunology
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacology*
Substances
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Adjuvants, Immunologic
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Galactosylceramides
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Ligands
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Triazoles
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alpha-galactosylceramide