New CD1d agonists: synthesis and biological activity of 6â³-triazole-substituted α-galactosyl ceramides.
Bioorg Med Chem Lett
; 22(13): 4348-52, 2012 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-22652050
ABSTRACT
Huisgen [3+2] dipolar cycloaddition of 6â³-azido-6â³-deoxy-α-galactosyl ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of triazole-containing α-galactosyl ceramide (α-GalCer) analogues in high yield. These α-GalCer analogues and the precursor azide 11 were tested for their ability to activate iNKT cells and stimulate IL-2 cytokine secretion in vitro, and IFN-γ and IL-4 cytokine secretion in vivo. Some of these analogues, specifically 11, 12b, 12f and 13, were more potent IL-2 stimulators than the prototypical CD1d agonist, α-GalCer 1. In terms of any cytokine bias, most of the triazole-containing analogues exhibited a small Th2 cytokine-biasing response relative to that shown by α-GalCer 1. In contrast, the cycloaddition precursor, namely azide 11, provided a small Th1 cytokine-biasing response.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Triazóis
/
Antígenos CD1d
/
Galactosilceramidas
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Reino Unido