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Interaction of chloramphenicol tripeptide analogs with ribosomes

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Abstract

Chloramphenicol amine peptide derivatives containing tripeptide fragments of regulatory “stop peptides”–MRL, IRA, IWP–were synthesized. The ability of the compounds to form ribosomal complexes was studied by displacement of the fluorescent erythromycin analog from its complex with E. coli ribosomes. It was found that peptide chloramphenicol analogs are able to bind to bacterial ribosomes. The dissociation constants were 4.3-10 μM, which is 100-fold lower than the corresponding values for chloramphenicol amine–ribosome complex. Interaction of the chloramphenicol peptide analogs with ribosomes was simulated by molecular docking, and the most probable contacts of “stop peptide” motifs with the elements of nascent peptide exit tunnel were identified.

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Abbreviations

Bhoc:

N-benzhydryloxycarbonyl

Boc:

tert-butyloxycarbonyl

BODIPY:

(4,4-difluoro-4-bora-5,7-dimethyl)-3a,4a-diaza-s-indacene-3-pentanoic acid

Caeg:

3-(2-aminoethyl)-3-[2-(cytosin-1-yl)acetyl]glycine

DCC:

1,3-dicyclohexylcarbodiimide

DIPEA:

diisopropylethylamine

Ery:

erythromycin

Fmoc:

fluorenylmethyloxycarbonyl

LCMS:

liquid chromatography-mass spectrometry

PNA:

peptide-nucleic acids

PTC:

peptidyl transferase center

RT:

ribosomal tunnel

TFA:

trifluoroacetic acid

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Authors and Affiliations

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

    A. G. Tereshchenkov, V. N. Tashlitsky, A. A. Bogdanov & N. V. Sumbatyan

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

    A. V. Shishkina, G. A. Korshunova & A. A. Bogdanov

Authors
  1. A. G. Tereshchenkov
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  2. A. V. Shishkina
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  3. V. N. Tashlitsky
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  4. G. A. Korshunova
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  5. A. A. Bogdanov
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  6. N. V. Sumbatyan
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Corresponding author

Correspondence to N. V. Sumbatyan.

Additional information

Published in Russian in Biokhimiya, 2016, Vol. 81, No. 4, pp. 538-547.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM15-322, January 31, 2016.

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Tereshchenkov, A.G., Shishkina, A.V., Tashlitsky, V.N. et al. Interaction of chloramphenicol tripeptide analogs with ribosomes. Biochemistry Moscow 81, 392–400 (2016). https://doi.org/10.1134/S000629791604009X

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  • DOI: https://doi.org/10.1134/S000629791604009X

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