Synthesis of Conformationally Constrained α-Galactosylceramide Analogues by exo-Glycal Chemistry and Evaluation of Biological Activity on Natural Killer T Cells
Date Issued
2007
Date
2007
Author(s)
Liao, Ching-Lun
DOI
zh-TW
Abstract
Natural killer T (NKT) cells are a novel subset of T cells that express both T-cell and natural killer (NK)-cell markers. NKT cells recognize non-classical MHC class I molecule CD1d in conjunction with glycolipid antigens. Among the reported glycolipids presented by human or mouse CD1d, α-galactosylceramide (α-GalCer) shows the highest immune-stimulatory activities. α-GalCer is derived from a marine sponge natural product and has been shown to possess antitumor activity. Further studies indicate that α-GalCer can bind to CD1d and activate NKT cells through T cell receptor (TCR) recognition to produce T helper 1 (TH1) and T helper 2 (TH2) cytokines, such as interferon-γ (IFN-γ) and interleukin-4 (IL-4), respectively.
Modification of α-GalCer may alter the level of stimulatory activity and/or switch the cytokine pattern released by NKT cells. Several reports have described the structural requirement for α-GalCer recognition by CD1d-restricted NKT cells, but few of them studied the effect of sugar conformation. Herein we designed and synthesized conformationally constrained α-GalCer analogues with different fatty acyl chains. The key step employs the glycosylation of exo-glycals, offering the advantage of exclusive stereoselectivity. We also evaluated their ability to activate mouse NKT cells by measuring cytokine release profiles.
Subjects
α-半乳糖神經醯胺
自然殺手T細胞
限制構形
α-Galactosylceramide
Natural Killer T Cells
Conformationally Constrained
SDGs
Type
other
File(s)![Thumbnail Image]()
Loading...
Name
ntu-96-R94b46034-1.pdf
Size
23.31 KB
Format
Adobe PDF
Checksum
(MD5):1c1eb6bf26110b6ec0d4d234be70b2ec