Rapid identification of immunostimulatory alpha-galactosylceramides using synthetic combinatorial libraries |
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| Authors: | Li Qian Ndonye Rachel M Illarionov Petr A Yu Karl O A Jerud Elliot S Diaz Kristine Bricard Gabriel Porcelli Steven A Besra Gurdyal S Chang Young-Tae Howell Amy R |
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| Institution: | Department of Chemistry, New York University, New York, New York 10003, USA. |
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| Abstract: | Two 60+-membered libraries of alpha-galactosylceramides have been prepared by reactions between activated ester resins and two core, fully deprotected galactosylated sphingoid bases. The libraries were evaluated for their ability to stimulate CD1d-restricted NKT cells, using in vitro stimulation of a murine NKT cell hybridoma line and for their ability to induce the expansion of NKT cells from peripheral blood mononuclear cells (PBMC) of a normal human subject. Our results showed that many compounds constructed on a C18-phytosphingosine base had significant stimulatory activity in both assays. Because no product purification was required, this approach is particularly attractive as a method for rapid synthesis of large libraries of potential immunomodulatory glycosylceramides. |
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