Synthesis of 6"-triazole-substituted α-GalCer analogues as potent iNKT cell stimulating ligands

Nora Pauwels; Sandrine Aspeslagh; Dirk Elewaut; Serge Van Calenbergh

doi:10.1016/j.bmc.2012.09.063

Synthesis of 6"-triazole-substituted α-GalCer analogues as potent iNKT cell stimulating ligands

Nora Pauwels, Sandrine Aspeslagh, Dirk Elewaut, Serge Van Calenbergh

Medical Oncology

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15 Citations (Scopus)

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.

Original language	English
Pages (from-to)	7149-7154
Number of pages	6
Journal	Bioorganic & Medicinal Chemistry
Volume	20
Issue number	24
DOIs	https://doi.org/10.1016/j.bmc.2012.09.063
Publication status	Published - 15 Dec 2012

Bibliographical note

Keywords

Adjuvants, Immunologic/chemical synthesis
Animals
Bone Marrow Cells/drug effects
Dendritic Cells/drug effects
Galactosylceramides/chemical synthesis
Ligands
Mice
Natural Killer T-Cells/drug effects
Triazoles/chemical synthesis

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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.",

keywords = "Adjuvants, Immunologic/chemical synthesis, Animals, Bone Marrow Cells/drug effects, Dendritic Cells/drug effects, Galactosylceramides/chemical synthesis, Ligands, Mice, Natural Killer T-Cells/drug effects, Triazoles/chemical synthesis",

author = "Nora Pauwels and Sandrine Aspeslagh and Dirk Elewaut and {Van Calenbergh}, Serge",

year = "2012",

month = dec,

day = "15",

doi = "10.1016/j.bmc.2012.09.063",

language = "English",

volume = "20",

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journal = "Bioorganic & Medicinal Chemistry",

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T1 - Synthesis of 6"-triazole-substituted α-GalCer analogues as potent iNKT cell stimulating ligands

AU - Pauwels, Nora

AU - Aspeslagh, Sandrine

AU - Elewaut, Dirk

AU - Van Calenbergh, Serge

PY - 2012/12/15

Y1 - 2012/12/15

N2 - 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.

AB - 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.

KW - Adjuvants, Immunologic/chemical synthesis

KW - Animals

KW - Bone Marrow Cells/drug effects

KW - Dendritic Cells/drug effects

KW - Galactosylceramides/chemical synthesis

KW - Ligands

KW - Mice

KW - Natural Killer T-Cells/drug effects

KW - Triazoles/chemical synthesis

U2 - 10.1016/j.bmc.2012.09.063

DO - 10.1016/j.bmc.2012.09.063

M3 - Article

C2 - 23122935

SN - 0968-0896

VL - 20

SP - 7149

EP - 7154

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 24

ER -

Synthesis of 6"-triazole-substituted α-GalCer analogues as potent iNKT cell stimulating ligands

Abstract

Bibliographical note

Keywords

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