通过炔烃与磺酰叠氮的偶联反应，以多样化合成GDP-岩藻糖类似物的方式开发α1,6-岩藻糖基转移酶抑制剂。

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

作者信息

Manabe Yoshiyuki, Kasahara Satomi, Takakura Yohei, Yang Xiaoxiao, Takamatsu Shinji, Kamada Yoshihiro, Miyoshi Eiji, Yoshidome Daisuke, Fukase Koichi

机构信息

Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.

Division of Health Sciences, Graduate School of Medicine, Osaka University, 1-7 Yamadaoka, Suita, Osaka 565-0871, Japan.

出版信息

Bioorg Med Chem. 2017 Jun 1;25(11):2844-2850. doi: 10.1016/j.bmc.2017.02.036. Epub 2017 Feb 28.

DOI:10.1016/j.bmc.2017.02.036

PMID:28284868

Abstract

We developed α1,6-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.

摘要

我们通过多样化导向合成开发了α1,6-岩藻糖基转移酶（FUT8）抑制剂。含炔烃的岩藻糖单元与含磺酰叠氮的鸟嘌呤单元在各种条件下的偶联反应得到了一系列5'-二磷酸鸟苷-β-L-岩藻糖（GDP-岩藻糖）类似物。合成的化合物表现出FUT8抑制活性。对接研究表明，与FUT8合成的抑制剂的结合模式与GDP-岩藻糖的相似。