抗生素开发的新靶点:核糖开关  

Novel targets for antibiotics discovery: riboswitches

作　　者：贾东方[1] 林俊生[1,2] 刁勇[1] 

机构地区：[1]华侨大学分子药物研究院,福建泉州362021 [2]新西兰农业研究院生殖与基因组中心

出　　处：《药学学报》2013年第9期1361-1368,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30973591;81270734;81271691);国家国际科技合作项目(2011DFG33320)

摘　　要：核糖开关是位于mRNA区域的特定片段,被小分子配体激活后即可顺式调控基因表达,无需蛋白参与。经进化选择,大部分细菌内核糖开关采用必需代谢产物为配体,负责调控与配体生物合成或转运相关基因的表达。代谢产物类似物可以抑制核糖开关介导的基因表达,抑制细菌生长,甚至引起细菌死亡,因此核糖开关可以作为抗生素开发的新靶点。已经发现的几种先导化合物显示了以核糖开关为靶点的开发潜力。本文简要阐述了可以作为抗生素靶点的核糖开关及其作用机制,介绍了以核糖开关为靶点的新型抗生素高通量筛选及药物设计方法,并对可能遇到的困难进行了分析。Riboswitches are cis-acting domains located in mRNA sequences that could regulate gene expression by sensing small molecules without employing protein. Most known riboswitches in bacteria have naturally evolved to bind essential metabolite ligands and are involved in the regulation of critical genes that are responsible for the biosynthesis or transport of the cognate ligand. The riboswitch-mediated gene expression could be repressed by metabolite analogs, which caused bacterial growth inhibition or even death. A number of leading compounds targeting riboswitches have been discovered. A promising avenue for the development of new class of riboswitch-based antibiotics has been opened. Herein we reviewed the current findings of riboswitches that served as targets for antibacterial drug development and the underlying mechanisms. The development of high-throughput methods and rational drug design for riboswitch-specific drug discovery are summarized. Relevant challenges are discussed.

关 键 词：核糖开关 耐药性 抗生素 

分 类 号：R963[医药卫生—微生物与生化药学]