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Synthesis of Glycolipids as Potential TLR4 Agonists
Thesis

Synthesis of Glycolipids as Potential TLR4 Agonists

黃立德
Masters, 國立清華大學, 化學系
2007

Abstract

Galcer TLR4 glycolipid
Toll-like receptor 4, commonly expressed in innate immune cells, is considered as one of promising molecular targets for immune – modulating drugs, because it can be activated to regulate immune response by ligand interaction. Our previous report shows that glycolipids with serine coupled with lipid amine to mimic phytosphingosine of □-GalCer, a bioactive glycolipid, can activate immune system via TLR4. Herein, we used amide bond formation to synthesize sixty new galactosyl serine derivatives efficiently. Moreover, we modified the sugar moiety of galactosyl serine derivatives, to achieve the synthesis of 14 different compounds. The assay results, tested in Dr. Shu-Ling Fu’s Laboratory, show that galactosyl serine lipids with lipid amine containing C11 and fatty acid containing C12 as well as four compounds with modified sugar moiety can activate human epithelial cell via TLR4. The results suggest that these derivatives are immune modulators and may serve as potential immunoadjuvant in immunotherapy.

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