Synthesis of C-5″ and C-6″-modified α-GalCer analogues as iNKT-cell agonists

Joren Guillaume; Nora Pauwels; Sandrine Aspeslagh; Dirk M Zajonc; Dirk Elewaut; Serge Van Calenbergh

doi:10.1016/j.bmc.2015.04.068

Synthesis of C-5″ and C-6″-modified α-GalCer analogues as iNKT-cell agonists

Joren Guillaume, Nora Pauwels, Sandrine Aspeslagh, Dirk M Zajonc, Dirk Elewaut, Serge Van Calenbergh

Medical Oncology

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Alpha-galactosyl ceramide (α-GalCer) is a prototypical synthetic ligand of invariant natural killer T (iNKT) cells. Upon presentation by the MHC class I-like molecule CD1d, this glycolipid stimulates iNKT cells to secrete a vast amount of both pro-inflammatory Th1 and anti-inflammatory Th2 cytokines. Recently, we discovered that selected 6″-modified α-GalCer analogues may produce markedly Th1-biased responses due to the formation of either an additional anchor with CD1d or by establishing extra interactions with the T-cell receptor of iNKT cells. Here, we report a practical synthesis towards 6″-O-carbamate and galacturonamide analogues of α-GalCer and their evaluation as iNKT cell agonists in mice.

Original language	English
Pages (from-to)	3175-3182
Number of pages	8
Journal	Bioorganic & Medicinal Chemistry
Volume	23
Issue number	13
DOIs	https://doi.org/10.1016/j.bmc.2015.04.068
Publication status	Published - 1 Jul 2015

Bibliographical note

Keywords

Animals
Antigen Presentation
Antigens, CD1d/genetics
Carbamates/chemistry
Carbohydrate Sequence
Crystallography, X-Ray
Galactosylceramides/chemical synthesis
Gene Expression
Hexuronic Acids/chemistry
Immunity, Innate
Interferon-gamma/biosynthesis
Interleukin-4/biosynthesis
Ligands
Mice
Mice, Inbred C57BL
Models, Molecular
Molecular Sequence Data
Natural Killer T-Cells/cytology
Protein Binding
Receptors, Antigen, T-Cell/genetics
Structure-Activity Relationship
Th1-Th2 Balance/drug effects

Access to Document

10.1016/j.bmc.2015.04.068

Handle.net

Persistent link

Cite this

@article{a8ab939ad6b24b129f2867ff311e1ea9,

title = "Synthesis of C-5″ and C-6″-modified α-GalCer analogues as iNKT-cell agonists",

abstract = "Alpha-galactosyl ceramide (α-GalCer) is a prototypical synthetic ligand of invariant natural killer T (iNKT) cells. Upon presentation by the MHC class I-like molecule CD1d, this glycolipid stimulates iNKT cells to secrete a vast amount of both pro-inflammatory Th1 and anti-inflammatory Th2 cytokines. Recently, we discovered that selected 6″-modified α-GalCer analogues may produce markedly Th1-biased responses due to the formation of either an additional anchor with CD1d or by establishing extra interactions with the T-cell receptor of iNKT cells. Here, we report a practical synthesis towards 6″-O-carbamate and galacturonamide analogues of α-GalCer and their evaluation as iNKT cell agonists in mice. ",

keywords = "Animals, Antigen Presentation, Antigens, CD1d/genetics, Carbamates/chemistry, Carbohydrate Sequence, Crystallography, X-Ray, Galactosylceramides/chemical synthesis, Gene Expression, Hexuronic Acids/chemistry, Immunity, Innate, Interferon-gamma/biosynthesis, Interleukin-4/biosynthesis, Ligands, Mice, Mice, Inbred C57BL, Models, Molecular, Molecular Sequence Data, Natural Killer T-Cells/cytology, Protein Binding, Receptors, Antigen, T-Cell/genetics, Structure-Activity Relationship, Th1-Th2 Balance/drug effects",

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

year = "2015",

month = jul,

day = "1",

doi = "10.1016/j.bmc.2015.04.068",

language = "English",

volume = "23",

pages = "3175--3182",

journal = "Bioorganic & Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "13",

}

TY - JOUR

T1 - Synthesis of C-5″ and C-6″-modified α-GalCer analogues as iNKT-cell agonists

AU - Guillaume, Joren

AU - Pauwels, Nora

AU - Aspeslagh, Sandrine

AU - Zajonc, Dirk M

AU - Elewaut, Dirk

AU - Van Calenbergh, Serge

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Alpha-galactosyl ceramide (α-GalCer) is a prototypical synthetic ligand of invariant natural killer T (iNKT) cells. Upon presentation by the MHC class I-like molecule CD1d, this glycolipid stimulates iNKT cells to secrete a vast amount of both pro-inflammatory Th1 and anti-inflammatory Th2 cytokines. Recently, we discovered that selected 6″-modified α-GalCer analogues may produce markedly Th1-biased responses due to the formation of either an additional anchor with CD1d or by establishing extra interactions with the T-cell receptor of iNKT cells. Here, we report a practical synthesis towards 6″-O-carbamate and galacturonamide analogues of α-GalCer and their evaluation as iNKT cell agonists in mice.

AB - Alpha-galactosyl ceramide (α-GalCer) is a prototypical synthetic ligand of invariant natural killer T (iNKT) cells. Upon presentation by the MHC class I-like molecule CD1d, this glycolipid stimulates iNKT cells to secrete a vast amount of both pro-inflammatory Th1 and anti-inflammatory Th2 cytokines. Recently, we discovered that selected 6″-modified α-GalCer analogues may produce markedly Th1-biased responses due to the formation of either an additional anchor with CD1d or by establishing extra interactions with the T-cell receptor of iNKT cells. Here, we report a practical synthesis towards 6″-O-carbamate and galacturonamide analogues of α-GalCer and their evaluation as iNKT cell agonists in mice.

KW - Animals

KW - Antigen Presentation

KW - Antigens, CD1d/genetics

KW - Carbamates/chemistry

KW - Carbohydrate Sequence

KW - Crystallography, X-Ray

KW - Galactosylceramides/chemical synthesis

KW - Gene Expression

KW - Hexuronic Acids/chemistry

KW - Immunity, Innate

KW - Interferon-gamma/biosynthesis

KW - Interleukin-4/biosynthesis

KW - Ligands

KW - Mice

KW - Mice, Inbred C57BL

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Natural Killer T-Cells/cytology

KW - Protein Binding

KW - Receptors, Antigen, T-Cell/genetics

KW - Structure-Activity Relationship

KW - Th1-Th2 Balance/drug effects

U2 - 10.1016/j.bmc.2015.04.068

DO - 10.1016/j.bmc.2015.04.068

M3 - Article

C2 - 26003341

SN - 0968-0896

VL - 23

SP - 3175

EP - 3182

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 13

ER -

Synthesis of C-5″ and C-6″-modified α-GalCer analogues as iNKT-cell agonists

Abstract

Bibliographical note

Keywords

Access to Document

Handle.net

Fingerprint

Cite this