Sarkar A K, Fritz T A, Taylor W H, Esko J D
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama, Birmingham 35294-0005, USA.
Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3323-7. doi: 10.1073/pnas.92.8.3323.
Inhibitors of glycosylation provide a tool for studying the biology of glycoconjugates. One class of inhibitors consists of glycosides that block glycoconjugate synthesis by acting as primers of free oligosaccharide chains. A typical primer contains one sugar linked to a hydrophobic aglycone. In this report, we describe a way to use disaccharides as primers. Chinese hamster ovary cells readily take up glycosides containing a pentose linked to naphthol, but they take up hexosides less efficiently and disaccharides not at all. Linking phenanthrol to a hexose improves its uptake dramatically but has no effect on disaccharides. To circumvent this problem, analogs of Xyl beta 1-->6Gal beta-O-2-naphthol were tested as primers of glycosaminoglycan chains. The unmodified disaccharide did not prime, but methylated derivatives had activity in the order Xyl beta 1-->6Gal(Me)3-beta-O-2-naphthol > Xyl beta 1-->6Gal (Me)2 beta-O-2-naphthol >> Xyl beta 1-->6Gal(Me)beta-O-2-naphthol. Acetylated Xyl beta 1-->6Gal beta-O-2-naphthol also primed glycosaminoglycans efficiently, suggesting that the terminal xylose residue was exposed by removing the acetyl groups. The general utility of using acetyl groups to create disaccharide primers was shown by the priming of oligosaccharides on peracetylated Gal beta 1-->4GlcNAc beta-O-naphthalenemethanol. This disaccharide inhibited sialyl Lewis X expression on HL-60 cells.
糖基化抑制剂为研究糖缀合物的生物学特性提供了一种工具。一类抑制剂由糖苷组成，这些糖苷通过充当游离寡糖链的引物来阻断糖缀合物的合成。典型的引物包含一个与疏水性苷元相连的糖。在本报告中，我们描述了一种使用二糖作为引物的方法。中国仓鼠卵巢细胞很容易摄取含有与萘酚相连的戊糖的糖苷，但摄取己糖苷的效率较低，而对二糖则完全不摄取。将菲咯醇与己糖相连可显著提高其摄取率，但对二糖没有影响。为了解决这个问题，测试了木糖β1→6半乳糖β - O - 2 - 萘酚的类似物作为糖胺聚糖链的引物。未修饰的二糖没有引发作用，但甲基化衍生物具有活性，活性顺序为木糖β1→6半乳糖（Me）3 - β - O - 2 - 萘酚＞木糖β1→6半乳糖（Me）2β - O - 2 - 萘酚＞＞木糖β1→6半乳糖（Me）β - O - 2 - 萘酚。乙酰化的木糖β1→6半乳糖β - O - 2 - 萘酚也能有效地引发糖胺聚糖的合成，这表明通过去除乙酰基，末端木糖残基得以暴露。通过对全乙酰化的半乳糖β1→4N - 乙酰葡糖胺β - O - 萘甲醇上的寡糖进行引发作用，证明了使用乙酰基来创建二糖引物的普遍实用性。这种二糖抑制了HL - 60细胞上唾液酸化路易斯X的表达。
