Abstract
4-Deoxy-alpha-GalCer analogues are considered weaker agonists than KRN7000 for the stimulation of human iNKT cells, but this remains strongly debated. In this work, we described a strategy toward 4-deoxy-alpha-GalCers with, as a key step, a metathesis reaction allowing sphingosine modifications from a single ethylenic alpha-galactoside precursor. The 4-deoxy-KRN7000 derivative 2, described here, induced potent cytokinic responses, comparable to those of KRN7000, both from human iNKT cells in vitro and from their murine counterpart in vivo.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adjuvants, Immunologic / chemical synthesis
-
Adjuvants, Immunologic / pharmacology*
-
Animals
-
Galactosylceramides / chemical synthesis
-
Galactosylceramides / pharmacology*
-
Humans
-
Interferon-gamma / biosynthesis
-
Interleukin-4 / biosynthesis
-
Lymphocyte Activation / drug effects*
-
Mice
-
Natural Killer T-Cells / drug effects*
-
Structure-Activity Relationship
-
Tumor Necrosis Factor-alpha / biosynthesis
Substances
-
Adjuvants, Immunologic
-
Galactosylceramides
-
Tumor Necrosis Factor-alpha
-
Interleukin-4
-
Interferon-gamma
-
KRN 7000