title: 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. 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.
authors: Department of Chemistry, New York University, New York, New York 10003, USA.
authors: Qian
authors: Q
authors: Li
authors: Rachel M
authors: RM
authors: Ndonye
authors: Petr A
authors: PA
authors: Illarionov
authors: Karl O A
authors: KO
authors: Yu
authors: Elliot S
authors: ES
authors: Jerud
authors: Kristine
authors: K
authors: Diaz
authors: Gabriel
authors: G
authors: Bricard
authors: Steven A
authors: SA
authors: Porcelli
authors: Gurdyal S
authors: GS
authors: Besra
authors: Young-Tae
authors: YT
authors: Chang
authors: Amy R
authors: AR
authors: Howell
mesh_terms: D000818:Animals; D020650:Combinatorial Chemistry Techniques; D005690:Galactose / Q000737:chemistry; D005699:Galactosylceramides / Q000138:chemical synthesis / Q000276:immunology* / Q000494:pharmacology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008956:Models, Chemical; D012117:Resins, Synthetic / Q000737:chemistry; D013107:Sphingolipids / Q000737:chemistry; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
chemical_list: D005699:Galactosylceramides; D012117:Resins, Synthetic; D013107:Sphingolipids; C493154:alpha-galactosylceramide; C012491:phytosphingosine; D013110:Sphingosine; D005690:Galactose