• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Current drug targets. Infectious disorders >New aminoacyl-tRNA synthetase inhibitors as antibacterial agents.
【24h】

New aminoacyl-tRNA synthetase inhibitors as antibacterial agents.

机译：新的氨酰基-tRNA合成酶抑制剂作为抗菌剂。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Increasing rates of bacterial resistance to known classes of antibiotics present a severe global challenge. As a consequence, the search for new chemical entities that address novel bacterial targets remains ongoing. Aminoacyl-tRNA synthetases (aa-RS) are essential enzymes for protein biosynthesis and emerged as an interesting target class in antibacterial research. These enzymes are present in all living organisms, and they are indispensable for the highly specific translation of the messenger-RNA (mRNA) template into protein via specific transfer-RNAs (tRNAs) as adapter molecules. When one aa-RS is inhibited, the corresponding tRNA is not charged and is therefore unavailable for translation. This leads to protein synthesis inhibition, which, in turn, causes cell growth arrest. Consequently, each compound that inhibits any of the aa-RS is a potential antibacterial agent. The clinical utility of this principle is proven by the natural product Ile-RS inhibitor pseudomonic acid, which is currently marketed as an antibacterial agent for topical application. Various chemical structures that inhibit aa-RS have been identified. These inhibitors have either been isolated from natural sources or have been generated synthetically. The synthetic inhibitors are modifications of natural inhibitors, derivatives of the natural synthetase substrates and reaction intermediates, or have been identified by screening of compound libraries. The recent progress achieved with these different classes of aa-RS inhibitors and their antibacterial potential in vitro and in vivo is discussed in this review.
机译：细菌对已知种类的抗生素的抗药性的增加提出了严峻的全球挑战。结果，寻找解决新细菌靶标的新化学实体的工作仍在进行中。氨酰基-tRNA合成酶（aa-RS）是蛋白质生物合成中必不可少的酶，在抗菌研究中作为有趣的靶标类出现。这些酶存在于所有活生物体中，它们对于使信使RNA（mRNA）模板通过特定的转移RNA（tRNA）作为衔接子分子高度特异性翻译成蛋白质是必不可少的。当一个aa-RS被抑制时，相应的tRNA不带电荷，因此不可用于翻译。这导致蛋白质合成抑制，进而导致细胞生长停滞。因此，抑制任何aa-RS的每种化合物都是潜在的抗菌剂。天然产物Ile-RS抑制剂假单酸证明了这一原理的临床实用性，目前已将其作为局部应用的抗菌剂进行销售。已经鉴定出抑制aa-RS的各种化学结构。这些抑制剂要么是从自然资源中分离出来的，要么是合成产生的。合成抑制剂是天然抑制剂的修饰，天然合成酶底物的衍生物和反应中间体，或已通过筛选化合物文库进行鉴定。本文综述了使用这些不同类型的aa-RS抑制剂及其在体外和体内的抗菌潜力所取得的最新进展。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号