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New fluorescent macrolide derivatives for studying interactions of antibiotics and their analogs with the ribosomal exit tunnel

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Abstract

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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Abbreviations

Aoc:

(aminooxy)acetic acid

Boc:

tert-butyloxycarbonyl

BODIPY:

4,4-difluoro-5,7-dimethyl-4-bora-3a,4adiaza-s-indacene-3-pentanoic acid (BODIPY FL C5)

DCC:

1,3-dicyindacenclohexylcarbodiimide

Des:

desmycosin

DIPEA:

diisopropylethylamine

Ery:

erythromycin

LC-MS:

chromatomass-spectrometry

NBD:

7-nitro-2,1,3-benzoxadiazole-4-yl

OMT:

5-O-mycaminosyltylonolide

RT:

ribosomal tunnel

TFA:

trifluoroacetic acid

Tyl:

tylosin

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Authors and Affiliations

  1. Faculty of Chemistry, Lomonosov Moscow State University, 119991, Moscow, Russia

    A. G. Tereshchenkov, V. V. Karpenko, V. A. Chertkov, A. A. Bogdanov & N. V. Sumbatyan

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

    A. V. Shishkina & A. A. Bogdanov

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

    A. L. Konevega & P. S. Kasatsky

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

    A. L. Konevega & P. S. Kasatsky

Authors
  1. A. G. Tereshchenkov
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  2. A. V. Shishkina
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  3. V. V. Karpenko
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  4. V. A. Chertkov
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  5. A. L. Konevega
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  6. P. S. Kasatsky
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  7. A. A. Bogdanov
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  8. N. V. Sumbatyan
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Correspondence to N. V. Sumbatyan.

Additional information

Published in Russian in Biokhimiya, 2016, Vol. 81, No. 10, pp. 1439–1450.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM16-186, September 12, 2016.

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10541_2016_323_MOESM1_ESM.pdf

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

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Tereshchenkov, A.G., Shishkina, A.V., Karpenko, V.V. et al. New fluorescent macrolide derivatives for studying interactions of antibiotics and their analogs with the ribosomal exit tunnel. Biochemistry Moscow 81, 1163–1172 (2016). https://doi.org/10.1134/S0006297916100138

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  • DOI: https://doi.org/10.1134/S0006297916100138

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