Mylvaganam M, Lingwood C A
Division of Immunity, Infection, Injury and Repair Research Institute, Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
Biochem Biophys Res Commun. 1999 Apr 13;257(2):391-4. doi: 10.1006/bbrc.1999.0474.
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 Gb3 showed significantly enhanced solubility in water compared to natural Gb3. Adamantyl-Gb3 showed a thousand fold enhanced inhibitory activity (IC50 = 1 microM) for VT-Gb3 binding as compared to a lipid free Gb3 oligosaccharide derivative, alphaGal1-4betaGal1-4betaGlc1-O-CH2CH(CH2SO2C 4H9)2 (IC50 > 2 mM). This represents a new approach to the generation of antagonists of glycolipid receptors.
球三糖神经酰胺（Gb3）与志贺毒素（VT）的相互作用是糖脂受体的几个例子之一，其中神经酰胺（或脂质）游离寡糖未能显示出预期的结合参数。我们提出了一种新颖但简单的策略来合成保留受体功能的单价水溶性糖鞘脂模拟物。用刚性的三维烃框架（如金刚烷）取代脂肪酸链，得到了一类新型的新烃糖缀合物。与天然Gb3相比，源自Gb3的此类金刚烷基缀合物在水中的溶解度显著提高。与无脂质的Gb3寡糖衍生物αGal1-4βGal1-4βGlc1-O-CH2CH(CH2SO2C4H9)2（IC50>2 mM）相比，金刚烷基-Gb3对VT-Gb3结合的抑制活性提高了一千倍（IC50 = 1 μM）。这代表了一种产生糖脂受体拮抗剂的新方法。
