New Fluorescent Macrolide Derivatives for Studying Interactions of Antibiotics and Their Analogs with the Ribosomal Exit Tunnel

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A. G. Tereshchenkov¹, A. V. Shishkina², V. V. Karpenko¹, V. A. Chertkov¹, A. L. Konevega^3,4, P. S. Kasatsky^3,4, A. A. Bogdanov^1,2 and N. V. Sumbatyan^1*

¹Lomonosov Moscow State University, Faculty of Chemistry, 119991 Moscow, Russia; E-mail: sumbtyan@belozersky.msu.ru

²Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991 Moscow, Russia

³Molecular and Radiation Biophysics Division, Konstantinov Petersburg Nuclear Physics Institute, National Research Center “Kurchatov Institute”, 188300 Gatchina, Russia

⁴Peter the Great Saint-Petersburg Polytechnic University, 195251 St. Petersburg, Russia

^* To whom correspondence should be addressed.

Received June 21, 2016; Revision received July 18, 2016

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Novel fluorescent derivatives of macrolide antibiotics related to tylosin bearing rhodamine, fluorescein, Alexa Fluor 488, BODIPY FL, and nitrobenzoxadiazole (NBD) residues were synthesized. The formation of complexes of these compounds with 70S E. coli ribosomes was studied by measuring the fluorescence polarization depending on the ribosome amount at constant concentration of the fluorescent substance. With the synthesized fluorescent tylosin derivatives, the dissociation constants for ribosome complexes with several known antibiotics and macrolide analogs previously obtained were determined. It was found that the fluorescent tylosin derivatives containing BODIPY FL and NBD groups could be used to screen the binding of novel antibiotics to bacterial ribosomes in the macrolide-binding site.

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KEY WORDS: macrolides, tylosin, fluorescent derivatives, nascent peptide exit tunnel, fluorescent polarization

DOI: 10.1134/S0006297916100138

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