Gama Cristal I, Tully Sarah E, Sotogaku Naoki, Clark Peter M, Rawat Manish, Vaidehi Nagarajan, Goddard William A, Nishi Akinori, Hsieh-Wilson Linda C
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Nat Chem Biol. 2006 Sep;2(9):467-73. doi: 10.1038/nchembio810. Epub 2006 Jul 30.
Although glycosaminoglycans contribute to diverse physiological processes, 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.
尽管糖胺聚糖参与多种生理过程,但由于无法获得同质的糖胺聚糖结构,对其分子机制的理解受到了阻碍。在这里,我们采用一种收敛性的合成方法组装了结构明确的硫酸软骨素寡糖,该方法允许在碳水化合物主链的精确位置安装硫酸基团。利用这些明确的结构,我们证明特定的硫酸化基序作为生长因子的分子识别元件发挥作用,并调节神经元生长。这些结果既提供了对硫酸化作用的基本见解,也为“硫酸化密码”提供了直接证据,即糖胺聚糖以类似于DNA、RNA和蛋白质的序列特异性方式编码功能信息。