Glycomic analysis of sialic acid linkages in glycans derived from blood serum glycoproteins.

Glycomic analysis of sialic acid linkages in glycans derived from blood serum glycoproteins.
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DOI:
10.1021/pr901210r
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发表时间:
2010-06-04
影响因子:
4.4
通讯作者:
Novotny, Milos V.
Novotny, Milos V.
中科院分区:
生物学2区
文献类型:
--
作者:
Alley, William R., Jr.;Novotny, Milos V.

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先前已经描述了许多疾病和病症的正常糖组学谱的许多改变,因此强调了研究与生物样品中存在的蛋白质相关的聚糖的医学重要性。癌症进展中的一个重要变化是α 2,6-唾液酸化水平增加,这有助于增加肿瘤细胞的转移潜力。在这里,我们报告了一种糖组学方法,选择性酰胺化α 2,6-连接的唾液酸,而那些是α 2,3-连接进行自发内酯化。在随后的全甲基化后,MALDI-TOF-MS分析显示,在乳腺癌样本中,血清中发现的糖蛋白上存在的许多唾液酸化聚糖的特征是α 2,6唾液酸化水平增加。基于α 2,3-连接唾液酸与α 2,6-连接唾液酸的比例改变,当仅基于传统糖组学分析时,这些聚糖中的许多聚糖不作为此类指标时,它们变得具有诊断相关性。
A number of alterations to the normal glycomic profile have been previously described for a number of diseases and disorders, thus underscoring the medical importance of studying the glycans associated with proteins present in biological samples. An important alteration in cancer progression is an increased level of α2,6-sialylation, which aids in increasing the metastatic potential of tumor cells. Here we report a glycomic method that selectively amidates α2,6-linked sialic acids, while those that are α2,3-linked undergo spontaneous lactonization. Following subsequent permethylation, MALDI-TOF-MS analysis revealed that many sialylated glycans present on glycoproteins found in blood serum featured increased levels of α2,6 sialylation in breast cancer samples. Based on the altered ratios of α2,3-linked to α2,6-linked sialic acids, many of these glycans became diagnostically relevant when they did not act as such indicators when based on traditional glycomic profiling alone.
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