Selection of the biological activity of DNJ neoglycoconjugates through click length variation of the side chain
Selection of the biological activity of DNJ neoglycoconjugates through click length variation of the side chain
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DOI：
10.1039/c1ob05119a
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发表时间：
2011-01-01
影响因子：
3.2
通讯作者：
Vauzeilles, Boris
中科院分区：
文献类型：
--
作者：
Ardes-Guisot, Nicolas;Alonzi, Dominic S.;Vauzeilles, Boris
通过与官能化金刚烷的点击连接，制备了一系列脱氧诺吉霉素衍生的新糖偶联物。它们已经被检测为糖苷酶抑制剂，作为与高谢病治疗相关的糖酶的抑制剂，以及与囊性纤维化有关的缺陷离子转运蛋白的纠正剂。我们已经证明，通过改变连接DNJ和金刚烷的烷基链的长度，可以选择性地强烈抑制ER-α-葡萄糖苷酶和神经酰胺葡萄糖基转移酶，或者恢复CF-KM4细胞中CFTR的活性。
A series of neoglycoconjugates derived from deoxynojirimycin has been prepared by click connection with functionalised adamantanes. They have been assayed as glycosidase inhibitors, as inhibitors of the glycoenzymes relevant to the treatment of Gaucher disease, as well as correctors of the defective ion-transport protein involved in cystic fibrosis. We have demonstrated that it is possible to selectively either strongly inhibit ER-alpha-glucosidases and ceramide glucosyltransferase or restore the activity of CFTR in CF-KM4 cells by varying the length of the alkyl chain linking DNJ and adamantane.