Detection and Modulation of Fucosylated Glycans using Fucose Analogs

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  • Kizuka Yasuhiko
    Center for Highly Advanced Integration of Nano and Life Sciences (G-CHAIN), Gifu University

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  • フコース誘導体を用いたフコシル化糖鎖の検出と改変
  • フコース ユウドウタイ オ モチイタ フコシルカ トウサ ノ ケンシュツ ト カイヘン

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Abstract

<p>Sugar analogs can be used as a probe for glycans or as inhibitors of glycosylation. Here, the actions of both existing and our own recently developed fucose analogs are described. Glycans containing fucose are involved in the pathology of diseases, including inflammation, COPD (chronic obstructive pulmonary disease) and cancer as well as basic biological phenomena, including development, immunity, and neural functions. Therefore, developing detection probes and inhibitors of fucosylation is desirable. Although several fucose analogs for detection and inhibition have been developed, these analogs have problems with sensitivity, toxicity, and potency. We have recently developed a highly sensitive probe for fucosylated glycans with low toxicity, “7-alkynyl-fucose.” This probe is a better substrate for various fucosyltransferases compared with an existing probe, leading to efficient incorporation into glycans and highly sensitive detection of glycans. In addition, we found that another fucose analog, “6-alkynyl-fucose,” is a potent inhibitor of fucosylation and has the potential to suppress cancer invasion. The mechanism of action was revealed to be selective inhibition of the GDP-fucose biosynthetic enzyme FX. These results show that fucose analogs are potentially powerful research tools, and a glyco-chemical biology approach toward the detection and inhibition of glycans using sugar analogs is expected to be developed in future.</p>

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