Synthesis of sugar-amino acid-nucleosides as potential glycosyltransferase inhibitors
Synthesis of sugar-amino acid-nucleosides as potential glycosyltransferase inhibitors
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DOI：
10.1016/j.bmc.2010.11.044
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发表时间：
2011-01-01
影响因子：
3.5
通讯作者：
Zou, Wei
中科院分区：
文献类型：
--
作者：
Vembaiyan, Kannan;Pearcey, Jean A.;Zou, Wei
糖-氨基酸-核苷(SAAN)是基于碱性氨基酸可能以类似于二磷酸金属离子络合物的方式与酶的羧基相互作用的假设而合成的，以模拟糖基核苷酸供体。选择D-半乳糖或L-阿拉伯呋喃糖环体系的C-糖苷类似物和四种氨基酸(赖氨酸、谷氨酰胺、色氨酸和组氨酸)进行了研究。这些靶标被合成，并针对GlfT2进行测试，GlfT2是结核分枝杆菌细胞壁半乳糖生物合成所必需的一种半乳糖呋喃糖基转移酶。抑制实验表明，含有组氨酸和色氨酸的类似物是GlfT2的中度抑制剂。皇冠版权所有(C)2010由爱思唯尔有限公司出版。保留所有权利。
Sugar-amino acid-nucleosides (SAAN) were synthesized to mimic glycosyl nucleotide donors based on the hypothesis that a basic amino acid may interact with carboxylate groups of the enzyme in a manner similar to the diphosphate metal ion complex. C-Glycoside analogues of the D-galactopyranose or L-arabinofuranose ring systems, and four amino acids (lysine, glutamine, tryptophan, and histidine), were chosen for this study. The targets were synthesized and tested against GlfT2, a galactofuranosyltransferase essential for cell wall galactan biosynthesis in Mycobacterium tuberculosis. The inhibition assay showed that analogues containing histidine and tryptophan are moderate inhibitors of GlfT2. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.