Adamantyl globotriaosyl ceramide: a monovalent soluble mimic which inhibits verotoxin binding to its glycolipid receptor.
Adamantyl globotriaosyl ceramide: a monovalent soluble mimic which inhibits verotoxin binding to its glycolipid receptor.
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金刚烷基三糖基神经酰胺：一种单价可溶性模拟物，可抑制维罗毒素与其糖脂受体的结合。
DOI：
10.1006/bbrc.1999.0474
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Lingwood,CA
中科院分区：
文献类型：
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作者：
Mylvaganam,M;Lingwood,CA
神经酰胺三己糖苷（Gb 3）与维罗毒素（VT）的相互作用是糖脂受体的几个实例之一，其中不含神经酰胺（或脂质）的寡糖未能显示预期的结合参数。我们提出了一种新的，但简单的策略来合成单价，水溶性鞘糖脂模拟物保留受体功能。用刚性的三维烃框架如金刚烷取代脂肪酸链，得到一类新的烃糖缀合物。与天然Gb 3相比，衍生自Gb 3的此类金刚烷基缀合物显示出显著增强的水中溶解度。金刚烷基-Gb 3对VT-Gb 3结合的抑制活性（IC 50 = 1 μM）比无脂Gb 3寡糖衍生物α Gal 1 - 4β Gal 1 - 4 β Glc 1-O-CH 2CH（CH 2SO 2C 4 H9）2（IC 50> 2 mM）高1000倍。这代表了产生糖脂受体拮抗剂的新方法。
The globotriaosylceramide (Gb3) verotoxin (VT) interaction is one of several examples of glycolipid receptors where the ceramide (or lipid) free oligosaccharides fail to show the expected binding parameters. We present a novel, yet simple strategy to synthesize monovalent, water soluble glycosphingolipid mimics which retain receptor function. Replacing the fatty acid chain with rigid, three dimensional hydrocarbon frames, such as adamantane, gives a novel class of neohydrocarbon glycoconjugates. Such adamantyl conjugates derived from Gb3showed significantly enhanced solubility in water compared to natural Gb3. Adamantyl-Gb3showed a thousand fold enhanced inhibitory activity (IC50= 1 μM) for VT-Gb3binding as compared to a lipid free Gb3oligosaccharide derivative, αGal1-4βGal1-4βGlc1-O-CH2CH(CH2SO2C4H9)2(IC50> 2 mM). This represents a new approach to the generation of antagonists of glycolipid receptors.