Fucosylation is a glycan modification critically involved in cancer and inflammation. Although potent fucosylation inhibitors are useful for basic and clinical research, only a few inhibitors have been developed. Here, we focus on a fucose analog with an alkyne group, 6-alkynyl-fucose (6-Alk-Fuc), which is used widely as a detection probe for fucosylated glycans, but is also suggested for use as a fucosylation inhibitor. Our glycan analysis using lectin and mass spectrometry demonstrated that 6-Alk-Fuc is a potent and general inhibitor of cellular fucosylation, with much higher potency than the existing inhibitor, 2-fluoro-fucose (2-F-Fuc). The action mechanism was shown to deplete cellular GDP-Fuc, and the direct target of 6-Alk-Fuc is FX (encoded byTSTA3), the bifunctional GDP-Fuc synthase. We also show that 6-Alk-Fuc halts hepatoma invasion. These results highlight the unappreciated role of 6-Alk-Fuc as a fucosylation inhibitor and its potential use for basic and clinical science.

中文翻译：

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炔基-岩藻糖通过抑制GDP-岩藻糖合成酶FX，TSTA3阻止肝癌细胞的迁移和侵袭。

岩藻糖基化是一种关键涉及癌症和炎症的聚糖修饰。尽管有效的岩藻糖基化抑制剂可用于基础和临床研究，但仅开发了几种抑制剂。在这里，我们重点研究带有炔基的岩藻糖类似物6-炔基岩藻糖（6-Alk-Fuc），它广泛用作岩藻糖基化聚糖的检测探针，但也建议用作岩藻糖基化抑制剂。我们使用凝集素和质谱进行的聚糖分析表明，6-Alk-Fuc是一种有效的细胞岩藻糖基化抑制剂，其效力远高于现有的抑制剂2-氟岩藻糖（2-F-Fuc）。已证明该作用机制消耗了细胞GDP-Fuc，而6-Alk-Fuc的直接靶标是双功能GDP-Fuc合酶FX（由TSTA3编码）。我们还显示6-Alk-Fuc阻止了肝癌的侵袭。