Zhou Jian, Wang Guannan, Zhang Li-He, Ye Xin-Shan
The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Med Res Rev. 2007 May;27(3):279-316. doi: 10.1002/med.20085.
The increased awareness of the central role of RNA has led to realization that RNA, as structural and functional information accumulation, is also drug target to small molecular therapy. Aminoglycosides are a group of well-known antibiotics, which function through binding to specific sites in prokaryotic ribosomal RNA (rRNA) and affecting the fidelity of protein synthesis. Unfortunately, their clinical practice has been curtailed by toxicity and rapid increasing number of resistant strains. Therefore, it is highly desirable to design new modified aminoglycosides that will overcome the undesirable properties of natural occurring aminoglycosides. On the other hand, aminoglycosides as potential antiviral (HIV) agents were also reported. Herein, we survey the current efforts to develop new aminoglycoside derivatives with modification and reconstruction on each sugar ring and review the latest advances in structure-activity relationships (SAR).
对RNA核心作用的认识不断提高，促使人们认识到RNA作为结构和功能信息的积累，也是小分子疗法的药物靶点。氨基糖苷类是一类著名的抗生素，它们通过与原核核糖体RNA（rRNA）中的特定位点结合并影响蛋白质合成的保真度来发挥作用。不幸的是，它们的临床应用因毒性和耐药菌株数量的迅速增加而受到限制。因此，非常需要设计新的修饰氨基糖苷类，以克服天然氨基糖苷类的不良特性。另一方面，也有报道称氨基糖苷类可作为潜在的抗病毒（HIV）药物。在此，我们综述了目前在每个糖环上进行修饰和改造以开发新的氨基糖苷类衍生物的努力，并回顾了构效关系（SAR）的最新进展。
