Novel lipid A mimetics derived from pentaerythritol: synthesis and their potent agonistic activity

被引：29

作者：

Jiang, ZH ^{[1
]}

Budzynski, WA ^{[1
]}

Skeels, LN ^{[1
]}

Krantz, MJ ^{[1
]}

Koganty, RR ^{[1
]}

机构：

[1] Biomira Inc, Edmonton, AB T6N 1H1, Canada

来源：

TETRAHEDRON | 2002年 / 58卷 / 43期

关键词：

lipid A mimetic; pentaerythritol; immunostimulatory adjuvant; cytokine; molecular vaccine;

D O I：

10.1016/S0040-4020(02)01067-0

中图分类号：

O62 [有机化学];

学科分类号：

070303 [有机化学]; 081704 [应用化学];

摘要：

A pentaerythritol unit is substituted for glucosamine as its functional mimic at the reducing end of lipid A disaccharide. Two such pentaerythritol derived lipid A mimetics 3 and 4, carrying three identical fatty acyl moieties, have been designed and synthesized. An efficient strategy, which involves simultaneous introduction of lipids onto two amino groups, is described for the synthesis of compounds 3 and 4. The biological activity profile of these two novel lipid A mimetics 3 and 4 is surprisingly similar to the natural lipid A product isolated from Salmonella minnesota R595. An in vitro cell activation assay, using human adherent antigen presenting cells, has demonstrated that both 3 and 4 induce the secretion of high levels of cytokines such as tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8. Also, in a totally synthetic liposomal vaccine system, 3 and 4 exhibit strong immunostimulatory adjuvant property in enhancing antigen specific T-cell activation. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：8833 / 8842

页数：10

共 43 条

[1]

Toll-like receptors: critical proteins linking innate and acquired immunity [J].