Construction of Sphingolipids Libraries and their Utilities

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  • PARK Jeong-Ju
    Department of Chemistry, Pohang University of Science & Technology
  • Yu Seok-Ho
    Department of Chemistry, Pohang University of Science & Technology
  • CHUNG Sung-Kee
    Department of Chemistry, Pohang University of Science & Technology

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Sphingolipids such as ceramide and glycosylceramide have recently attracted intense research interests because of their roles as signalling molecules in many important physiological processes, such as apoptosis, inflammation and immune responses. Their well-defined modular structures are ideally amenable to library formation for medicinal chemistry investigations. We have developed practical, divergent synthetic routes to sphingosine and phytosphingosine isomers as well as to carba-sugar analogues of all D-aldohexopyranose isomers toward these goals. And then we have proceeded to prepare ceramide libraries, composed of more than 500 compounds each, based on these sphingosine and phytosphingosine isomers, and demonstrated their utility in cell-based bioassays involving activation of NF- KB and induction of apoptosis. We are also in the process of forming libraries of mono-glycosylceramide and mono-carba-glycosylceramide.

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