Jia Dong-fang, Jia Dong-fang, Jia Dong-fang
Institute of Molecular Medicine, Huaqiao University, Quanzhou 362021, China.
Yao Xue Xue Bao. 2013 Sep;48(9):1361-8.
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 relevant challenges are discussed. summarized.
核糖开关是位于mRNA序列中的顺式作用结构域,其可通过感应小分子来调节基因表达而无需借助蛋白质。细菌中大多数已知的核糖开关已自然进化为结合必需代谢物配体,并参与对负责同源配体生物合成或转运的关键基因的调控。核糖开关介导的基因表达可被代谢物类似物抑制,这会导致细菌生长抑制甚至死亡。已经发现了许多靶向核糖开关的先导化合物。开发新型基于核糖开关的抗生素的一条有前景的途径已经开启。在此,我们综述了作为抗菌药物开发靶点的核糖开关的当前研究结果及其潜在机制。还讨论了用于核糖开关特异性药物发现的高通量方法和合理药物设计的相关挑战并进行了总结。