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Biochemistry (Moscow)

, Volume 81, Issue 10, pp 1163–1172 | Cite as

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

  • A. G. Tereshchenkov
  • A. V. Shishkina
  • V. V. Karpenko
  • V. A. Chertkov
  • A. L. Konevega
  • P. S. Kasatsky
  • A. A. Bogdanov
  • N. V. SumbatyanEmail author
Article

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.

Key words

macrolides tylosin fluorescent derivatives nascent peptide exit tunnel fluorescent polarization 

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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Supplementary material

10541_2016_323_MOESM1_ESM.pdf (371 kb)
New Fluorescent Macrolide Derivatives for Studying Interactions of Antibiotics and Their Analogs with the Ribosomal Exit Tunnel

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Copyright information

© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  • A. G. Tereshchenkov
    • 1
  • A. V. Shishkina
    • 2
  • V. V. Karpenko
    • 1
  • V. A. Chertkov
    • 1
  • A. L. Konevega
    • 3
    • 4
  • P. S. Kasatsky
    • 3
    • 4
  • A. A. Bogdanov
    • 1
    • 2
  • N. V. Sumbatyan
    • 1
    Email author
  1. 1.Faculty of ChemistryLomonosov Moscow State UniversityMoscowRussia
  2. 2.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  3. 3.Molecular and Radiation Biophysics Division, Konstantinov Petersburg Nuclear Physics InstituteNational Research Center “Kurchatov Institute”GatchinaRussia
  4. 4.Peter the Great Saint-Petersburg Polytechnic UniversitySt. PetersburgRussia

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