Interaction of Chloramphenicol Cationic Peptide Analogues with the Ribosome

Virtual screening of all possible tripeptide analogues of chloramphenicol was performed using molecular docking to evaluate their affinity to bacterial ribosomes. Chloramphenicol analogues that demonstrated the lowest calculated energy of interaction with ribosomes were synthesized. Chloramphenicol...

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Bibliographic Details
Published in:Biochemistry (Moscow) 2020-11, Vol.85 (11), p.1443-1457
Main Authors: Khairullina, Z. Z., Tereshchenkov, A. G., Zavyalova, S. A., Komarova, E. S., Lukianov, D. A., Tashlitsky, V. N., Osterman, I. A., Sumbatyan, N. V.
Format: Article
Language:English
Subjects:
Affinity
Amino acids
Antiinfectives and antibacterials
Antimicrobial agents
Antimicrobial peptides
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Biosynthesis
Chloramphenicol
Chloromycetin
Derivatives
E coli
Erythromycin
Fluorescence
Life Sciences
Mathematical analysis
Microbiology
Molecular docking
Peptides
Proline
Protein biosynthesis
Ribosomes
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Summary:Virtual screening of all possible tripeptide analogues of chloramphenicol was performed using molecular docking to evaluate their affinity to bacterial ribosomes. Chloramphenicol analogues that demonstrated the lowest calculated energy of interaction with ribosomes were synthesized. Chloramphenicol amine (CAM) derivatives, which contained specific peptide fragments from the proline-rich antimicrobial peptides were produced. It was demonstrated using displacement of the fluorescent erythromycin analogue from its complex with ribosomes that the novel peptide analogues of chloramphenicol were able to bind bacterial ribosome; all the designed tripeptide analogues and one of the chloramphenicol amine derivatives containing fragment of the proline-rich antimicrobial peptides exhibited significantly greater affinity to Escherichia coli ribosome than chloramphenicol. Correlation between the calculated and experimentally evaluated levels of the ligand efficiencies was observed. In vitro protein biosynthesis inhibition assay revealed, that the RAW-CAM analogue shows activity at the level of chloramphenicol. These data were confirmed by the chemical probing assay, according to which binding pattern of this analogue in the nascent peptide exit tunnel was similar to chloramphenicol.
ISSN:0006-2979
1608-3040
DOI:10.1134/S0006297920110127