Mycobacterial arabinan biosynthesis: the use of synthetic arabinoside acceptors in the development of an arabinosyl transfer assay
Mycobacterial arabinan biosynthesis: the use of synthetic arabinoside acceptors in the development of an arabinosyl transfer assay
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DOI：
10.1093/glycob/7.8.1121
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发表时间：
1997-12-01
期刊：
影响因子：
4.3
通讯作者：
Besra, GS
中科院分区：
文献类型：
--
作者：
Lee, RE;Brennan, PJ;Besra, GS
关于结核分枝杆菌细胞壁的D-阿拉伯聚糖的生物合成的信息正在迅速出现，并有望成为抗结核药物开发的新靶点。因此，利用合成的[1-C-14]-β-D-阿拉伯呋喃糖基-1-单磷酰癸烯醇作为供体和多种O-和S-烷基阿拉伯糖苷作为受体，开发了阿拉伯糖基转移酶测定法。α-D-Araf-（1->5）-α-D-Araf-O-和-S-烷基二阿拉伯糖苷和α-D-Araf-（1->5）-α-D-Araf-（1-> 5）-α-D-Araf-O-和-S-烷基三阿拉伯糖苷，而O-和S-烷基单糖受体无活性，O-和S-烷基二糖和O-和S-烷基三糖受体（5）阿拉伯糖基转移酶和β-D-阿拉伯呋喃糖基-1-单磷酰癸烯醇：阿拉伯聚糖β（1->2）阿拉伯糖基转移酶。β（1->2）阿拉伯糖基转移酶活性在O-烷基二糖受体存在下更明显，而两种转移酶在S-烷基三糖受体存在下大致相当。结核病药物乙胺丁醇（一种已知的分枝杆菌阿拉伯糖基转移酶抑制剂）在这些基于阿拉伯糖基转移酶/受体的测定系统中无活性，支持了第三种活性的其他证据，负责形成α 1->3连接，是药物的靶点。
Information on the biosynthesis of the D-arabinans of the cell wall of Mycobacterium tuberculosis is rapidly emerging, with the promise of new targets for drug development against tuberculosis, Accordingly, arabinosyl transferase assays were developed utilizing synthesized [1-C-14]-beta-D-arabinofuranosyl-1-monophosphoryldecaprenol as donor and a variety of O- and S-alkyl arabinosides as accepters, These were: alpha-D-Araf-(1-->5)-alpha-D-Araf-O- and -S-alkyl diarabinosides and alpha-D-Araf-(1-->5)-alpha-D-Araf-(1-->5)-alpha-D-Araf-O- and -S-alkyl triarabinosides, Whereas the O- and S-alkyl monosaccharide accepters were inactive, the O- and S-alkyl disaccharide and the O- and S-alkyl trisaccharide accepters (5) arabinosyl transferase and beta-D-arabinofuranosyl-1-monophosphoryldecaprenol: arabinan beta(1-->2) arabinosyl transferase. The beta(1-->2) arabinosyl transferase activity was more in evidence in the presence of the O-alkyl disaccharide acceptor, whereas both transferases were about equivalent in the presence of the S-alkyl trisaccharide acceptor, The tuberculosis drug, ethambutol, a known mycobacterial arabinosyl transferase inhibitor, was inactive within these arabinosyl transferase/accepter based assay systems, supporting other evidence that a third activity, responsible for the formation of alpha 1-->3 linkage, is the drug target.