Synthesis of α-GalCer and analogs
Date Issued
2010
Date
2010
Author(s)
Wu, Bing-Ching
Abstract
α-Galactosyl Ceramide（also called α-GalCer），was originally discovered by the Pharmaceutical Division of the Kirn Brewery Company during a screen for reagents derived from the marine sponge Agelas mauritianus in 1993, and has showed potential antitumor activity. However, in Phase I study, α-GalCer was ineffective in the treatment of tumor. When α-GalCer bound to CD1d, it activated NKT cells to produced T help 1（Th1） and T help 2（Th2） cytokines, such as Interferon-γ （IFN-γ）and Interleukin 4（IL-4）. Both cytokines were hindered by each other, and thus gave no benefit.
α-GalCer consisted of galactose, fatty acids and phytosphingosine. Our lab tried to synthesize many derivatives by computer modeling and evaluated the biological activities. The results showed synthetic glycolipid analogs which contained an aromatic ring in the acyl tail or sphingosine tail were more effective than α-GalCer in inducing Th1 cytokines.
In this thesis, I tried to modify the α-GalCer by fluorination of 5’- and 4’- hydroxyl group of the galactosyl moiety, and strengthen the glycosyl bonds. These analogs may increase the selectivity toward either Th1 or Th2 cytokines responses, and have great anticancer efficacy and other immune-enhancing activities than α-GalCer itself.
Subjects
醣脂類化合物
自然免疫殺手T細胞
Type
thesis
File(s)![Thumbnail Image]()
Loading...
Name
ntu-99-R94223082-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):a4e3d78143e22f10fa829a4666b54712