DISACCHARIDE UPTAKE AND PRIMING IN ANIMAL-CELLS - INHIBITION OF SIALYL-LEWIS-X BY ACETYLATED GAL-BETA-1-]4GLCNAC-BETA-O-NAPHTHALENEMETHANOL
DISACCHARIDE UPTAKE AND PRIMING IN ANIMAL-CELLS - INHIBITION OF SIALYL-LEWIS-X BY ACETYLATED GAL-BETA-1-]4GLCNAC-BETA-O-NAPHTHALENEMETHANOL
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DOI：
10.1073/pnas.92.8.3323
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发表时间：
1995-04-11
影响因子：
11.1
通讯作者：
ESKO, JD
中科院分区：
文献类型：
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作者：
SARKAR, AK;FRITZ, TA;ESKO, JD
糖基化抑制剂为研究糖复合物的生物学提供了工具。一类抑制剂由糖苷组成，它们通过充当游离寡糖链的引物来阻断糖缀合物的合成。典型的引物含有与疏水性糖苷配基连接的一种糖。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吸收含有与萘酚连接的戊糖的糖苷，但它们吸收己糖苷的效率较低，而根本不吸收二糖。将菲酚与己糖连接可显着提高其吸收，但对二糖没有影响。为了解决这个问题，测试了 Xyl beta 1-->6Gal beta-O-2-naphthol 的类似物作为糖胺聚糖链的引物。未修饰的二糖不引发，但甲基化衍生物的活性顺序为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。乙酰化的 Xyl beta 1-->6Gal beta-O-2-naphthol 也能有效地引发糖胺聚糖，表明末端木糖残基通过去除乙酰基而暴露。通过在全乙酰化 Gal beta 1-->4GlcNAc beta-O-萘甲醇上引发寡糖，显示了使用乙酰基创建二糖引物的一般实用性。这种二糖抑制 HL-60 细胞上唾液酸 Lewis X 的表达。
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.