Sulfation patterns of glycosaminoglycans encode molecular recognition and activity
Sulfation patterns of glycosaminoglycans encode molecular recognition and activity
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DOI：
10.1038/nchembio810
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发表时间：
2006-09-01
影响因子：
14.8
通讯作者：
Hsieh-Wilson, Linda C.
中科院分区：
文献类型：
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作者：
Gama, Cristal I.;Tully, Sarah E.;Hsieh-Wilson, Linda C.
虽然糖胺聚糖有助于不同的生理过程（1-4），但由于无法获得均匀的糖胺聚糖结构，对其分子机制的理解受到阻碍。在这里，我们组装了定义明确的硫酸软骨素寡糖使用收敛，合成方法，允许安装硫酸基团在精确的位置沿着碳水化合物主链。使用这些定义的结构，我们证明了特定的硫酸化基序的功能作为生长因子的分子识别元件和调节神经元的生长。这些结果提供了对硫酸化作用的基本认识和“硫酸化密码”的直接证据，其中糖胺聚糖以类似于DNA、RNA和蛋白质的序列特异性方式编码功能信息。
Although glycosaminoglycans contribute to diverse physiological processes(1-4), an understanding of their molecular mechanisms has been hampered by the inability to access homogeneous glycosaminoglycan structures. Here, we assembled well-defined chondroitin sulfate oligosaccharides using a convergent, synthetic approach that permits installation of sulfate groups at precise positions along the carbohydrate backbone. Using these defined structures, we demonstrate that specific sulfation motifs function as molecular recognition elements for growth factors and modulate neuronal growth. These results provide both fundamental insights into the role of sulfation and direct evidence for a `sulfation code' whereby glycosaminoglycans encode functional information in a sequence-specific manner analogous to that of DNA, RNA and proteins.