Faculty of Chemistry, Lomonosov Moscow State University, Moscow, 119991, Russia.
South Ural State University, Chelyabinsk, 454080, Russia.
Biochemistry (Mosc). 2022 Sep;87(9):871-889. doi: 10.1134/S0006297922090024.
Design and synthesis of conjugates consisting of the macrolide antibiotic desmycosin and fragments of the antibacterial peptide oncocin were performed in attempt to develop new antimicrobial compounds. New compounds were shown to bind to the E. coli 70S ribosomes, to inhibit bacterial protein synthesis in vitro, as well as to suppress bacterial growth. The conjugates of N-terminal hexa- and tripeptide fragments of oncocin and 3,2',4''-triacetyldesmycosin were found to be active against some strains of macrolide-resistant bacteria. By simulating molecular dynamics of the complexes of these compounds with the wild-type bacterial ribosomes and with ribosomes, containing A2059G 23S RNA mutation, the specific structural features of their interactions were revealed.
设计并合成了由大环内酯类抗生素去甲交沙霉素和抗菌肽 oncocin 的片段组成的缀合物，试图开发新的抗菌化合物。新化合物被证明能够与大肠杆菌 70S 核糖体结合，体外抑制细菌蛋白质合成，并抑制细菌生长。发现 oncocin 的 N 端六肽和三肽片段与 3,2',4''-三乙酰去甲交沙霉素的缀合物对一些大环内酯类耐药菌菌株具有活性。通过模拟这些化合物与野生型细菌核糖体以及含有 A2059G 23S RNA 突变的核糖体复合物的分子动力学，揭示了它们相互作用的特定结构特征。
