Rapid identification of immunostimulatory α-galactosylceramides using synthetic combinatorial libraries

Q Li; RM Ndonye; Petr Illarionov; KOA Yu; ES Jerud; K Diaz; G Bricard; SA Porcelli; Gurdyal Besra; YT Chang; AR Howell

doi:10.1021/cc070057i

Rapid identification of immunostimulatory α-galactosylceramides using synthetic combinatorial libraries

Q Li, RM Ndonye, Petr Illarionov, KOA Yu, ES Jerud, K Diaz, G Bricard, SA Porcelli, Gurdyal Besra, YT Chang, AR Howell

Biosciences

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12 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1084-1093
Number of pages	10
Journal	Journal of Combinatorial Chemistry
Volume	9
DOIs	https://doi.org/10.1021/cc070057i
Publication status	Published - 12 Nov 2007

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10.1021/cc070057i

Modulation of Immune Responses by aGalCer Analogues Through Differential Activation of CD1d-restricted NKT Cells
Besra, D. (Principal Investigator) & Lammas, T. (Co-Investigator)
Medical Research Council
1/06/05 → 30/11/09
Project: Research Councils

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title = "Rapid identification of immunostimulatory α-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.",

author = "Q Li and RM Ndonye and Petr Illarionov and KOA Yu and ES Jerud and K Diaz and G Bricard and SA Porcelli and Gurdyal Besra and YT Chang and AR Howell",

year = "2007",

month = nov,

day = "12",

doi = "10.1021/cc070057i",

language = "English",

volume = "9",

pages = "1084--1093",

journal = "Journal of Combinatorial Chemistry",

publisher = "American Chemical Society",

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

AU - Li, Q

AU - Ndonye, RM

AU - Illarionov, Petr

AU - Yu, KOA

AU - Jerud, ES

AU - Diaz, K

AU - Bricard, G

AU - Porcelli, SA

AU - Besra, Gurdyal

AU - Chang, YT

AU - Howell, AR

PY - 2007/11/12

Y1 - 2007/11/12

N2 - 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.

AB - 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.

U2 - 10.1021/cc070057i

DO - 10.1021/cc070057i

M3 - Article

C2 - 17896821

VL - 9

SP - 1084

EP - 1093

JO - Journal of Combinatorial Chemistry

JF - Journal of Combinatorial Chemistry

ER -

Rapid identification of immunostimulatory α-galactosylceramides using synthetic combinatorial libraries

Abstract

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Modulation of Immune Responses by aGalCer Analogues Through Differential Activation of CD1d-restricted NKT Cells

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