Disaccharide analogs as probes for glycosyltransferases in Mycobacterium tuberculosis
Disaccharide analogs as probes for glycosyltransferases in Mycobacterium tuberculosis
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DOI：
10.1016/j.bmc.2007.04.012
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发表时间：
2007-08-15
影响因子：
3.5
通讯作者：
Reynolds, Robert C.
中科院分区：
文献类型：
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作者：
Pathak, Ashish K.;Pathaka, Vibha;Reynolds, Robert C.
糖基转移酶(GTS)在分枝杆菌细胞壁的生物合成中起着至关重要的作用，是分枝杆菌生存所必需的。因此，这些酶是治疗结核病，特别是耐多药结核病(MDR-TB)的潜在新药靶点。本文报道了具有5-N，N-二甲氨基萘-L-磺胺乙基(丹氨基)单元的Araf(α1->；5)Araf、Ga1f(β1->；5)Galf和Galf(beta 1->；6)GalF二糖的高效合成，它们分别作为阿拉伯糖基和半乳糖转移酶的荧光二糖受体。与放射性标记的受体或供体相比，此类类似物可为酶的研究、分析开发和化合物筛选提供优势。此外，还制备了具有5-叠氮-1-磺胺乙基的类似物作为光亲和探针，用于研究结核分枝杆菌(MTB)中GTS(阿拉伯糖基和半乳糖基)的活性部位标记。除了它们的制备外，还介绍了作为糖基转移酶受体的这些二糖的初步生物学测试和动力学分析。(C)2007爱思唯尔有限公司。保留所有权利。
Glycosyltransferases (GTs) play a crucial role in mycobacterial cell wall biosynthesis and are necessary for the survival of mycobacteria. Hence, these enzymes are potential new drug targets for the treatment of tuberculosis (TB), especially multiple drug-resistant TB (MDR-TB). Herein, we report the efficient syntheses of Araf(alpha 1 -> 5)Araf, Ga1f(beta 1 -> 5)Galf and Galf(beta 1 -> 6)Galf disaccharides possessing a 5-N,N-dimethylaminonaphthalene-l-sulfonamidoethyl (dansyl) unit that were prepared as fluorescent disaccharide acceptors for arabinosyl- and galactosyl-transferases, respectively. Such analogs may offer advantages relative to radiolabeled acceptors or donors for studying the enzymes and for assay development and compound screening. Additionally, analogs possessing a 5-azidonaphthalene-1-sulfonamidoethyl unit were prepared as photoaffinity probes for then-potential utility in studying active site labeling of the GTs (arabinosyl and galactosyl) in MYcobacterium tuberculosis (MTB). Beyond their preparation, initial biological testing and kinetic analysis of these disaccharides as acceptors toward glycosyltransferases are also presented. (C) 2007 Elsevier Ltd. All rights reserved.