Divergent Chemoenzymatic Synthesis of Asymmetrical-Core-Fucosylated and Core-Unmodified N-Glycans.
Divergent Chemoenzymatic Synthesis of Asymmetrical-Core-Fucosylated and Core-Unmodified N-Glycans.
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DOI：
10.1002/chem.201604999
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发表时间：
2016-12-23
期刊：
影响因子：
--
通讯作者：
Boons GJ
中科院分区：
文献类型：
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作者：
Li T;Huang M;Liu L;Wang S;Moremen KW;Boons GJ
本文描述了一种从一种常见的先进前体制备核心岩藻糖基化和核心未修饰的不对称N-聚糖的趋异化学酶法。通过正交保护的核心岩藻糖基化六糖的连续化学糖基化合成十一糖，所述核心岩藻糖基化六糖是所有哺乳动物核心岩藻糖基化N-聚糖所共有的。使用一组糖基转移酶对十一碳糖进行双酶选择性酶促延伸，得到核心岩藻糖基化的不对称三触角N-聚糖异构体，这是乳腺癌的潜在生物标志物。我们的方法的一个独特方面是，已经鉴定了岩藻糖苷酶（FucA 1），其可以选择性地切割核心岩藻糖苷而不影响唾液酸化LewisX表位的岩藻糖苷，从而容易获得核心未修饰的化合物。
A divergent chemoenzymaytic approach for the preparation of core-fucosylated and core-unmodified asymmetrical N-glycans from a common advances precursor is described. An undecasaccharide was synthesized by sequential chemical glycosylations of an orthogonally protected core fucosylated hexasaccharide that is common to all mammalian core fucosylated N-glycans. Antennae-selective enzymatic extension of the undecasaccharide using a panel of glycosyl transferases afforded core fucosylated asymmetrical triantennary N-glycan isomers, which are potential biomarkers for breast cancer. A unique aspect of our approach is that a fucosidase (FucA1) has been identified that selectively can cleave a core-fucoside without affecting the fucoside of a sialyl LewisX epitope to give easy access to core-unmodified compounds.