Good L, Nielsen P E
Center for Biomolecular Recognition, Departments of Medical Biochemistry and Genetics, Biochemistry B, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Copenhagen, Denmark.
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2073-6. doi: 10.1073/pnas.95.5.2073.
Peptide nucleic acid (PNA) is a DNA mimic that has shown considerable promise as a lead compound for developing gene therapeutic drugs. We report that PNAs targeted to functional and accessible sites in ribosomal RNA can inhibit translation in an Escherichia coli cell-free transcription/translation system, with 50% reductions caused by nanomolar PNA concentrations. The effect in vitro is quantitatively similar to that of the known translation inhibitor and antibiotic tetracycline. Also, the targeted PNAs inhibited bacterial growth on agar plates and in liquid culture. A strain of E. coli (AS19) that is more permeable to antibiotics was approximately 10-fold more sensitive to the active PNAs, suggesting that the effect on growth indeed was caused by PNAs that entered cells. Inhibition was not observed when using control PNAs of similar composition but with an unrelated or mismatched sequence. The results demonstrate that ribosomal RNA is a possible target for sequence-designed novel antibiotics based on DNA analogues or mimics.
肽核酸（PNA）是一种模拟DNA的物质，作为开发基因治疗药物的先导化合物已展现出巨大潜力。我们报告称，靶向核糖体RNA功能且可及位点的PNA能够在大肠杆菌无细胞转录/翻译系统中抑制翻译，纳摩尔浓度的PNA可导致50%的抑制率。体外实验效果在定量上与已知的翻译抑制剂及抗生素四环素相似。此外，靶向PNA还能抑制琼脂平板和液体培养中的细菌生长。对抗生素渗透性更强的大肠杆菌菌株（AS19）对活性PNA的敏感性约高10倍，这表明对生长的抑制确实是由进入细胞的PNA引起的。使用组成相似但序列不相关或错配的对照PNA时未观察到抑制作用。结果表明，核糖体RNA可能是基于DNA类似物或模拟物的序列设计新型抗生素的一个靶点。
