Development of α1,6-fucosyltransferase inhibitors through the diversity-oriented syntheses of GDP-fucose mimics using the coupling between alkyne and sulfonyl azide

Publication date: Available online 28 February 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Yoshiyuki Manabe, Satomi Kasahara, Yohei Takakura, Xiaoxiao Yang, Shinji Takamatsu, Yoshihiro Kamada, Eiji Miyoshi, Daisuke Yoshidome, Koichi Fukase
We developed α 1,6-fucosyltransferase (FUT8) inhibitors through a diversity-oriented synthesis. The coupling reaction between the fucose unit containing alkyne and the guanine unit containing sulfonyl azide under various conditions afforded a series of Guanosine 5′-diphospho-β-L-fucose (GDP-fucose) analogs. The synthesized compounds displayed FUT8 inhibition activity. A docking study revealed that the binding mode of the inhibitor synthesized with FUT8 was similar to that of GDP-fucose.

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