Rapid identification of immunostimulatory alpha-galactosylceramides using synthetic combinatorial libraries

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. bur 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.