Selective inhibition of glycosyltransferases by bivalent imidazolium salts
Selective inhibition of glycosyltransferases by bivalent imidazolium salts
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DOI：
10.1016/j.bmc.2012.12.034
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发表时间：
2013-03-01
影响因子：
3.5
通讯作者：
Brockhausen, Inka
中科院分区：
文献类型：
--
作者：
Gao, Yin;Vlahakis, Jason Z.;Brockhausen, Inka
半乳糖基转移酶（GalTs）通过在末端的GlcNAc残基上添加Gal来延长哺乳动物糖蛋白的聚糖链，从而构建具有重要生物学意义的聚糖结构的支架。我们已经证明，带正电荷的二价咪唑盐，其中两个咪唑基团由20或22个碳的脂肪链连接，形成纯化的人β 3-GalT5的有效抑制剂，使用GlcNAc β -苄基作为受体底物。这些抑制剂不是底物类似物，也抑制了一些其他的糖基转移酶。这些双咪唑类化合物代表了一类新的糖基转移酶抑制剂，具有抗癌和抗炎的潜力。(C) 2013 Elsevier Ltd.版权所有。
Galactosyltransferases (GalTs) extend the glycan chains of mammalian glycoproteins by adding Gal to terminal GlcNAc residues, and thus build the scaffolds for biologically important glycan structures. We have shown that positively charged bivalent imidazolium salts in which the two imidazolium groups are linked by an aliphatic chain of 20 or 22 carbons form potent inhibitors of purified human beta 3-GalT5, using GlcNAc beta-benzyl as acceptor substrate. The inhibitors are not substrate analogs and also inhibited a selected number of other glycosyltransferases. These bis-imidazolium compounds represent a new class of glycosyltransferase inhibitors with potential as anti-cancer and anti-inflammatory drugs. (C) 2013 Elsevier Ltd. All rights reserved.