Rapid identification of immunostimulatory α-galactosylceramides using synthetic combinatorial libraries

Qian Li; Rachel M. Ndonye; Petr A. Illarionov; Karl O.A. Yu; Elliot S. Jerud; Kristine Diaz; Gabriel Bricard; Steven A. Porcelli; Gurdyal S. Besra; Young Tae Chang; Amy R. Howell

doi:10.1021/cc070057i

Rapid identification of immunostimulatory α-galactosylceramides using synthetic combinatorial libraries

Qian Li, Rachel M. Ndonye, Petr A. Illarionov, Karl O.A. Yu, Elliot S. Jerud, Kristine Diaz, Gabriel Bricard, Steven A. Porcelli, Gurdyal S. Besra, Young Tae Chang, Amy R. Howell

Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Two 60+-membered libraries of α-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.

Original language	English (US)
Pages (from-to)	1081-1093
Number of pages	13
Journal	Journal of Combinatorial Chemistry
Volume	9
Issue number	6
DOIs	https://doi.org/10.1021/cc070057i
State	Published - 2007

ASJC Scopus subject areas

Chemistry(all)

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10.1021/cc070057i

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title = "Rapid identification of immunostimulatory α-galactosylceramides using synthetic combinatorial libraries",

abstract = "Two 60+-membered libraries of α-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.",

author = "Qian Li and Ndonye, {Rachel M.} and Illarionov, {Petr A.} and Yu, {Karl O.A.} and Jerud, {Elliot S.} and Kristine Diaz and Gabriel Bricard and Porcelli, {Steven A.} and Besra, {Gurdyal S.} and Chang, {Young Tae} and Howell, {Amy R.}",

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T1 - Rapid identification of immunostimulatory α-galactosylceramides using synthetic combinatorial libraries

AU - Li, Qian

AU - Ndonye, Rachel M.

AU - Illarionov, Petr A.

AU - Yu, Karl O.A.

AU - Jerud, Elliot S.

AU - Diaz, Kristine

AU - Bricard, Gabriel

AU - Porcelli, Steven A.

AU - Besra, Gurdyal S.

AU - Chang, Young Tae

AU - Howell, Amy R.

PY - 2007

Y1 - 2007

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AB - Two 60+-membered libraries of α-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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Rapid identification of immunostimulatory α-galactosylceramides using synthetic combinatorial libraries

Abstract

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