Synthesis and biological activity of alpha-glucosyl C24:0 and C20:2 ceramides

Peter Jervis; Natacha Veerapen; G Bricard; Liam Cox; SA Porcelli; Gurdyal Besra

doi:10.1016/j.bmcl.2010.05.010

Synthesis and biological activity of alpha-glucosyl C24:0 and C20:2 ceramides

Peter Jervis, Natacha Veerapen, G Bricard, Liam Cox, SA Porcelli, Gurdyal Besra

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Abstract

a-Glucosyl ceramides 4 and 5 have been synthesised and evaluated for their ability to stimulate the activation and expansion of human iNKT cells. The key challenge in the synthesis of both target molecules was the stereoselective synthesis of the a-glycosidic linkage. Of the methods examined, glycosylation using per-TMS-protected glucosyl iodide 16 was completely a-selective and provided gram quantities of amine 11, from which a-glucosyl ceramides 4 and 5 were obtained by N-acylation. a-GlcCer 4, containing a C24 saturated acyl chain, stimulated a marked proliferation and expansion of human circulating iNKT cells in short-term cultures. a-GlcCer 5, which contains a C20 11,14-cis-diene acyl chain (C20:2),induced extremely similar levels of iNKT cell activation and expansion.

Original language	English
Pages (from-to)	3475-3478
Number of pages	4
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	20
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2010.05.010
Publication status	Published - 1 Jun 2010

Keywords

Antigen
Ceramide
iNKT
Lipid
CD1d

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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

Cite this

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title = "Synthesis and biological activity of alpha-glucosyl C24:0 and C20:2 ceramides",

abstract = "a-Glucosyl ceramides 4 and 5 have been synthesised and evaluated for their ability to stimulate the activation and expansion of human iNKT cells. The key challenge in the synthesis of both target molecules was the stereoselective synthesis of the a-glycosidic linkage. Of the methods examined, glycosylation using per-TMS-protected glucosyl iodide 16 was completely a-selective and provided gram quantities of amine 11, from which a-glucosyl ceramides 4 and 5 were obtained by N-acylation. a-GlcCer 4, containing a C24 saturated acyl chain, stimulated a marked proliferation and expansion of human circulating iNKT cells in short-term cultures. a-GlcCer 5, which contains a C20 11,14-cis-diene acyl chain (C20:2),induced extremely similar levels of iNKT cell activation and expansion.",

keywords = "Antigen, Ceramide, iNKT, Lipid, CD1d",

author = "Peter Jervis and Natacha Veerapen and G Bricard and Liam Cox and SA Porcelli and Gurdyal Besra",

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doi = "10.1016/j.bmcl.2010.05.010",

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TY - JOUR

T1 - Synthesis and biological activity of alpha-glucosyl C24:0 and C20:2 ceramides

AU - Jervis, Peter

AU - Veerapen, Natacha

AU - Bricard, G

AU - Cox, Liam

AU - Porcelli, SA

AU - Besra, Gurdyal

PY - 2010/6/1

Y1 - 2010/6/1

N2 - a-Glucosyl ceramides 4 and 5 have been synthesised and evaluated for their ability to stimulate the activation and expansion of human iNKT cells. The key challenge in the synthesis of both target molecules was the stereoselective synthesis of the a-glycosidic linkage. Of the methods examined, glycosylation using per-TMS-protected glucosyl iodide 16 was completely a-selective and provided gram quantities of amine 11, from which a-glucosyl ceramides 4 and 5 were obtained by N-acylation. a-GlcCer 4, containing a C24 saturated acyl chain, stimulated a marked proliferation and expansion of human circulating iNKT cells in short-term cultures. a-GlcCer 5, which contains a C20 11,14-cis-diene acyl chain (C20:2),induced extremely similar levels of iNKT cell activation and expansion.

AB - a-Glucosyl ceramides 4 and 5 have been synthesised and evaluated for their ability to stimulate the activation and expansion of human iNKT cells. The key challenge in the synthesis of both target molecules was the stereoselective synthesis of the a-glycosidic linkage. Of the methods examined, glycosylation using per-TMS-protected glucosyl iodide 16 was completely a-selective and provided gram quantities of amine 11, from which a-glucosyl ceramides 4 and 5 were obtained by N-acylation. a-GlcCer 4, containing a C24 saturated acyl chain, stimulated a marked proliferation and expansion of human circulating iNKT cells in short-term cultures. a-GlcCer 5, which contains a C20 11,14-cis-diene acyl chain (C20:2),induced extremely similar levels of iNKT cell activation and expansion.

KW - Antigen

KW - Ceramide

KW - iNKT

KW - Lipid

KW - CD1d

U2 - 10.1016/j.bmcl.2010.05.010

DO - 10.1016/j.bmcl.2010.05.010

M3 - Article

C2 - 20529677

VL - 20

SP - 3475

EP - 3478

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 12

ER -

Synthesis and biological activity of alpha-glucosyl C24:0 and C20:2 ceramides

Abstract

Keywords

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

Cite this