Howard Hughes Medical Institute, Waksman Institute, and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
Curr Opin Microbiol. 2011 Oct;14(5):532-43. doi: 10.1016/j.mib.2011.07.030. Epub 2011 Aug 19.
A new drug target - the 'switch region' - has been identified within bacterial RNA polymerase (RNAP), the enzyme that mediates bacterial RNA synthesis. The new target serves as the binding site for compounds that inhibit bacterial RNA synthesis and kill bacteria. Since the new target is present in most bacterial species, compounds that bind to the new target are active against a broad spectrum of bacterial species. Since the new target is different from targets of other antibacterial agents, compounds that bind to the new target are not cross-resistant with other antibacterial agents. Four antibiotics that function through the new target have been identified: myxopyronin, corallopyronin, ripostatin, and lipiarmycin. This review summarizes the switch region, switch-region inhibitors, and implications for antibacterial drug discovery.
一个新的药物靶点——“开关区域”，已经在细菌 RNA 聚合酶（RNAP）中被鉴定出来，该酶介导细菌 RNA 的合成。该新靶点是结合抑制细菌 RNA 合成并杀死细菌的化合物的结合位点。由于新的靶点存在于大多数细菌物种中，因此与该新靶点结合的化合物对广泛的细菌物种具有活性。由于新的靶点与其他抗菌剂的靶点不同，因此与该新靶点结合的化合物与其他抗菌剂没有交叉耐药性。已经确定了四种通过新靶点起作用的抗生素：粘菌素、珊瑚菌素、利帕他汀和脂酰霉素。这篇综述总结了开关区域、开关区域抑制剂以及对抗菌药物发现的意义。
