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Novel chloramphenicol peptide derivatives: design, synthesis and antibacterial activityтезисы доклада
- Авторы: Andrei Tereshchenkov, Vasilina Sergeeva, Anna Shishkina, Natalia Sumbatyan, Alexey Bogdanov
- Сборник: Abstracts of papers presented at the EMBO Conference Series Chemical Biology 2014
- Тезисы
- Год издания: 2014
- Место издания: Mera Druck GmbH Sanghausen, Germany
- Первая страница: 263
- Последняя страница: 263
- Аннотация: Recent ribosomal study outlines that nascent peptide chain (NC) can influence translation. Interactions of NC with the specific sites of ribosomal tunnel (RT) can be studied by means of low-molecular peptidyl-tRNA analogues. Previously we have designed a number of peptide-macrolide derivatives where the peptide part modeled the NC and antibiotic served as an “anchor” for positioning the peptide at the specific site of RT [1]. Now we report the new chloramphenicol peptide derivatives as analogues of the peptidyl-tRNA. Chloramphenicol inhibits protein synthesis by binding to the A-site of the peptidyl transferase center of bacterial ribosomes. X-ray data of the ribosome–chloramphenicol complex elucidates that dichloroacetic moiety of antibiotic is localized in the RT entrance and, consequently, if being replaced with peptide residue can mimic NC. These derivatives are usefull tools for studies of the NC interactions with the RT specific sites and their influence on the translation [2]. Moreover, these compounds are of interest as new antibacterials. Docking-based virtual screening of all amino acid, di- and tripeptide chloramphenicol derivatives was performed by means of the AutoDock Vina software to select the substances that effectively bind to the RT. The most interesting substances including chloramphenicol derivatives modified with different amino acids and short “stop-peptides” were synthesized. These compounds were examined for binding ability to bacterial ribosomes by displacement of fluorescently labeled erythromycin from its complex with E. coli ribosome and for the translation inhibition in vitro. This study was supported by the Russian Foundation for Basic Researches (13-04-00986-a, 13-04-40211-Н). 1. Shishkina A, Makarov G, Tereshchenkov A, Korshunova G, Sumbatyan N, Golovin A, Svetlov M, Bogdanov A. Bioconjug Chem, 2013, 24: 1861-9. 2. Mamos P, Krokidis MG, Papadas A, Karahalios P, Starosta AL, Wilson DN, Kalpaxis DL, Dinos GP. Biochimie, 2013, 95: 1765-72.
- Добавил в систему: Сумбатян Наталия Владимировна