Interaction of Chloramphenicol Cationic Peptide Analogues with the Ribosome

Autor:	Ilya A. Osterman, S A Zavyalova, Ekaterina S. Komarova, Andrey G Tereshchenkov, N.V. Sumbatyan, Vadim N. Tashlitsky, Zimfira Z Khairullina, Dmitrii A. Lukianov
Rok vydání:	2020
Předmět:	chemistry.chemical_classification 0303 health sciences Chemistry Stereochemistry Chloramphenicol 030302 biochemistry & molecular biology Antimicrobial peptides Peptide General Medicine Tripeptide Ligand (biochemistry) medicine.disease_cause Biochemistry Ribosome Molecular Docking Simulation 03 medical and health sciences medicine Protein biosynthesis Escherichia coli Peptides Ribosomes medicine.drug
Zdroj:	Biochemistry. Biokhimiia. 85(11)
ISSN:	1608-3040
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::82a92ee45429e736d27bb7d99cca334b https://pubmed.ncbi.nlm.nih.gov/33280584 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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