title: Synthesis of 6"-triazole-substituted α-GalCer analogues as potent iNKT cell stimulating ligands.
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.
authors.affiliation: Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Harelbekestraat 72, B-9000 Gent, Belgium.
authors.forename: Nora
authors.initials: N
authors.lastname: Pauwels
authors.forename: Sandrine
authors.initials: S
authors.lastname: Aspeslagh
authors.forename: Dirk
authors.initials: D
authors.lastname: Elewaut
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D051379:Mice; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D005699:Galactosylceramides; D008024:Ligands; D014230:Triazoles; C493154:alpha-galactosylceramide