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

被引：21

作者：

Jervis, Peter J. ^{[1
]}

Veerapen, Natacha ^{[1
]}

Bricard, Gabriel ^{[3
]}

Cox, Liam R. ^{[2
]}

Porcelli, Steven A. ^{[3
]}

Besra, Gurdyal S. ^{[1
]}

机构：

[1] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England

[2] Univ Birmingham, Sch Chem, Birmingham B15 2TT, W Midlands, England

[3] Yeshiva Univ, Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 12期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

CD1d; iNKT; Antigen; Ceramide; Lipid; NKT CELLS; EFFICIENT SYNTHESIS; ANALOGS; ACTIVATION; INNATE;

D O I：

10.1016/j.bmcl.2010.05.010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

alpha-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 alpha-glycosidic linkage. Of the methods examined, glycosylation using per-TMS-protected glucosyl iodide 16 was completely alpha-selective and provided gram quantities of amine 11, from which alpha-glucosyl ceramides 4 and 5 were obtained by N-acylation. alpha-GlcCer 4, containing a C24 saturated acyl chain, stimulated a marked proliferation and expansion of human circulating iNKT cells in short-term cultures. alpha-GlcCer 5, which contains a C20 11,14-cis-diene acyl chain (C20: 2), induced extremely similar levels of iNKT cell activation and expansion. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：3475 / 3478

页数：4

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