Structure-activity relationship studies of Bz amide-containing α-GalCer derivatives as natural killer T cell modulators.
CD1d
Glycolipid
Structure-activity relationships
α-GalCer
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 04 2019
15 04 2019
Historique:
received:
26
12
2018
revised:
18
02
2019
accepted:
18
02
2019
pubmed:
3
3
2019
medline:
11
3
2020
entrez:
3
3
2019
Statut:
ppublish
Résumé
CD1d is a non-polymorphic antigen-presenting glycoprotein that recognizes glycolipids as ligands. Ligands bind to the hydrophobic grooves of CD1d, and the resulting ligand-CD1d complexes activate natural killer T (NKT) cells by means of T cell receptor recognition, leading to the secretion of various cytokines. However, details of the ligand recognition mechanism of a large hydrophobic ligand binding pocket and the relationship between cytokine induction and ligand structure are unclear. We report the synthesis of α-GalCer derivatives containing a Bz amide group having various substituting groups in the ceramide moiety, and the analysis of the structure-activity relationships. The assays reveal that the Bz amide-containing CD1d ligands function as NKT cell modulators displaying Th2 cytokine biasing responses. Furthermore, molecular dynamics simulation studies suggest that the phenyl groups can interact with the aromatic amino acid residues in the lipid binding pocket of CD1d.
Identifiants
pubmed: 30824201
pii: S0960-894X(19)30102-7
doi: 10.1016/j.bmcl.2019.02.018
pii:
doi:
Substances chimiques
Amides
0
Antigens, CD1d
0
Cytokines
0
Galactosylceramides
0
Ligands
0
alpha-galactosylceramide
0
Benzene
J64922108F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
970-973Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.