2South Ural State University, 454080 Chelyabinsk, Russia
3Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia
4Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia
5Skolkovo Institute of Science and Technology, 143025 Skolkovo, Russia
6Faculty of Fundamental Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia
* To whom correspondence should be addressed.
Received May 20, 2022; Revised June 17, 2022; Accepted June 18, 2022
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.
KEY WORDS: macrolides, peptide derivatives, antimicrobial peptides, ribosome, molecular dynamics simulations, nascent peptide exit tunnel