Cellular metabolism of unnatural sialic acid precursors.
Cellular metabolism of unnatural sialic acid precursors.
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DOI：
10.1007/s10719-015-9593-7
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发表时间：
2015-10
影响因子：
3
通讯作者：
Kohler JJ
中科院分区：
文献类型：
--
作者：
Pham ND;Fermaintt CS;Rodriguez AC;McCombs JE;Nischan N;Kohler JJ
碳水化合物除了具有代谢功能外，还在多种生物过程中扮演着受体、配体和结构分子的重要角色。代谢低聚糖工程(MOE)有助于深入了解碳水化合物的生物学和机制。在MOE中，具有新官能团的非天然碳水化合物类似物被结合到细胞糖共轭中，用于探索生物系统。虽然教育部扩大了碳水化合物生物学的知识，但非天然碳水化合物类似物的有限新陈代谢限制了它的使用。在这里，我们评估了SiaDAz及其细胞通透性前体Ac4ManNDAz的代谢，SiaDAz是一种经二氮嗪修饰的唾液酸类似物。我们发现Ac4ManNDAz和SiaDAz的代谢效率取决于细胞类型。我们的结果表明，不同的细胞系在合成细胞表面SiaDAz的过程中可能有不同的代谢障碍。这些发现指出了细胞内酯酶、激酶和磷酸酶在非自然糖代谢中的作用，并为改善MOE的方法提供了指导。
Carbohydrates, in addition to their metabolic functions, serve important roles as receptors, ligands, and structural molecules for diverse biological processes. Insight into carbohydrate biology and mechanisms has been aided by metabolic oligosaccharide engineering (MOE). In MOE, unnatural carbohydrate analogs with novel functional groups are incorporated into cellular glycoconjugates and used to probe biological systems. While MOE has expanded knowledge of carbohydrate biology, limited metabolism of unnatural carbohydrate analogs restricts its use. Here we assess metabolism of SiaDAz, a diazirine-modified analog of sialic acid, and its cell-permeable precursor, Ac4ManNDAz. We show that the efficiency of Ac4ManNDAz and SiaDAz metabolism depends on cell type. Our results indicate that different cell lines can have different metabolic roadblocks in the synthesis of cell surface SiaDAz. These findings point to roles for promiscuous intracellular esterases, kinases, and phosphatases during unnatural sugar metabolism and provide guidance for ways to improve MOE.