Synthesis and evaluation of stimulatory properties of Sphingomonadaceae glycolipids

Department of Chemistry and Biochemistry, C100 BNSN, Brigham Young University, Provo, Utah 84602, USA.
Nature Chemical Biology (Impact Factor: 13.22). 07/2007; 3(9):559-564. DOI: 10.1038/nchembio.2007.19

ABSTRACT Glycosphingolipids (GSLs) from the Sphingomonadaceae family of bacteria have been reported to be potent stimulators of natural killer T cells. These glycolipids include mono-, tri- and tetraglycosylceramides. Here we have prepared the GSL-1 to GSL-4 series of glycolipids and tested their abilities to stimulate natural killer T cells. Among these glycolipids, only GSL-1 (Compound 1) is a potent stimulator. Using a series of synthetic diglycosylceramides, we show that oligoglycosylceramides from Sphingomonadaceae are not effectively truncated to GSL-1 in lysosomes in antigen-presenting cells, possibly because the higher-order GSLs are poor substrates for lysosomal acyltransfer enzymes.

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Available from: Shenglou Deng, Oct 25, 2014
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    • "The immunomodulatory activities of the two sphingomonads presented in this study also do not come as a surprise. Glycosphingolipids are a class of compounds that have been shown to serve as immunomodulatory agents (Long et al. 2007). The substance KRN7000, a synthetic analog of the natural product agelasphin 9b from the sponge Agelas mauritianus, is one such example and is currently in clinical trials for its capacity to stimulate NKT cells (Park et al. 2010). "
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    Marine Biotechnology 10/2011; 13(5):883-92. DOI:10.1007/s10126-010-9349-0 · 3.15 Impact Factor
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    • "However, strong activity also noted with β-lactosylarchaeol is encouraging for vaccine development in view of the low cost of lactose to serve as a readily available synthetic precursor. Also encouraging is the relatively simple synthesis reported herein using biosynthetic archaeol and carbohydrate precursors, compared to the multistep synthesis of other adjuvants such as glycosphingolipids (Long et al. 2007), QS-21A (Wang et al. 2005), or lipidA mimetics (Bazin et al. 2006). β-Lactosylarchaeol, for example, is synthesized from archaeol and lactose precursors in four synthetic steps. "
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    Glycobiology 08/2008; 18(7):559-65. DOI:10.1093/glycob/cwn038 · 3.14 Impact Factor
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    • "We are not certain why the weak reactivity to GSL-4A was not observed, but the CD1d coated plate assay is highly sensitive, and the A20 B cell transfectants we used express very high amounts of CD1d. Our results are consistent, however, with the finding that GSL-4A could not be processed to GSL-1 because APC lack the enzyme to cleave the N-glucosamine that GSL-4A contains (Long et al., 2007). GSL-4B apparently also could not be efficiently processed to generate GSL-1. "
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