Rapid Identification of Immunostimulatory alpha-Galactosylceramides Using Synthetic Combinatorial Libraries

摘要

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.