Probing the specificity of aminoglycoside ribosomal RNA interactions with designed synthetic analogs
Probing the specificity of aminoglycoside ribosomal RNA interactions with designed synthetic analogs
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DOI：
10.1021/ja972599h
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发表时间：
1998-03-11
影响因子：
15
通讯作者：
Wong, CH
中科院分区：
文献类型：
--
作者：
Alper, PB;Hendrix, M;Wong, CH
新霉素B和相关的氨基糖苷类抗生素的原核核糖体RNA解码区的结合已被调查使用最近开发的表面等离子体共振分析。含有新霉胺或新霉胺样亚结构的许多天然存在的氨基糖苷类特异性结合到核糖体解码区RNA的位点的模型。这种识别事件是这类化合物抗菌活性的基础。设计并合成了一系列类似物，以探索新霉素环IV（2，6-二脱氧-2，6-二氨基-β-L-艾杜糖吡喃）的作用。结合结果表明，艾杜糖环上的正电荷是体外特异性结合所必需的，并且不能被通过柔性接头连接的胺取代。然而，在针对大肠杆菌的液体培养测定中，环IV被st二胺尾替换的类似物的抗生素活性（最小抑制浓度）与新霉素B相同。
The binding of neomycin B and related aminoglycoside antibiotics to the prokaryotic ribosomal RNA decoding region has been investigated using a recently developed surface plasmon resonance assay. A number of naturally occurring aminoglycosides containing a neamine or neamine-like substructure bind specifically to a model of the site of the ribosomal decoding region RNA. This recognition event is the basis of the antibacterial activity of this class of compounds. A series of analogs was designed and synthesized to probe the role of neomycin ring IV (2,6-dideoxy-2,6-diamino-beta-L-idopyrano The binding results indicate that the positive charge presented on the idose ring is necessary for specific binding in vitro and cannot be replaced by amines attached via flexible linkers. However, the antibiotic activity (minimum inhibitory concentration) of the analog where ring IV is replaced with st diamine tail is the same as neomycin B in a liquid culture assay against Escherichia coli.