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

Autor:	Joren Guillaume, Dirk Elewaut, Nora Pauwels, Sandrine Aspeslagh, Dirk M. Zajonc, Serge Van Calenbergh
Přispěvatelé:	Medical Oncology
Rok vydání:	2015
Předmět:	Models Molecular Natural Killer T-Cells/cytology Clinical Biochemistry Gene Expression Pharmaceutical Science Crystallography X-Ray Ligands Biochemistry Antigens CD1d/genetics ACTIVATION Mice chemistry.chemical_compound Drug Discovery CRYSTAL-STRUCTURE PROTECTION Receptor Th1-Th2 Balance iNKT-cells Antigen Presentation NKT CELLS biology Chemistry Hexuronic Acids CD1D Natural killer T cell PHASE-I Carbohydrate Sequence Molecular Medicine lipids (amino acids peptides and proteins) Galactosylceramides/chemical synthesis GALACTOSYLCERAMIDE Protein Binding Ceramide Receptors Antigen T-Cell/genetics Molecular Sequence Data Receptors Antigen T-Cell Galactosylceramides chemical and pharmacologic phenomena Major histocompatibility complex Article Interferon-gamma Structure-Activity Relationship alpha-GalCer Interferon-gamma/biosynthesis Glycolipid Th1-Th2 Balance/drug effects MHC class I Animals Molecular Biology KRN7000 KILLER T-CELLS Interleukin-4/biosynthesis Organic Chemistry T-cell receptor Biology and Life Sciences Carbamates/chemistry Immunity Innate Mice Inbred C57BL carbohydrates (lipids) biology.protein Natural Killer T-Cells Carbamates Interleukin-4 Antigens CD1d Glycolipids LIGAND Hexuronic Acids/chemistry
Zdroj:	BIOORGANIC & MEDICINAL CHEMISTRY
ISSN:	0968-0896
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6497502e5a3999f5624f254e349f110d https://doi.org/10.1016/j.bmc.2015.04.068 Zobrazit plný text záznamu Full Text from ScienceDirect