Enzymatic Synthesis of Vancomycin-Modified DNA

Many potent antibiotics fail to treat bacterial infections due to emergence of drug-resistant strains. This surge of antimicrobial resistance (AMR) calls in for the development of alternative strategies and methods for the development of drugs with restored bactericidal activities. In this context,...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2022-12, Vol.27 (24), p.8927
Main Authors: Figazzolo, Chiara, Bonhomme, Frédéric, Saidjalolov, Saidbakhrom, Ethève-Quelquejeu, Mélanie, Hollenstein, Marcel
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Antibiotics
Antimicrobial agents
Antimicrobial resistance
Aptamers
Aptamers, Nucleotide - pharmacology
Bacterial diseases
Bacterial infections
Biofilms
Chemical Sciences
DNA
DNA biosynthesis
DNA polymerase
DNA polymerases
DNA-Directed DNA Polymerase - metabolism
Drug delivery systems
Drug development
Drug resistance
Drug resistance in microorganisms
Enzymatic synthesis
Enzymes
Health aspects
Medicinal Chemistry
Methicillin
modified nucleic acids
nucleoside triphosphates
Nucleosides
Nucleotide analogs
Nucleotides
Oligonucleotides
Organic chemistry
Pathogens
primer extension reactions
SELEX
SELEX Aptamer Technique - methods
Staphylococcus infections
Vancomycin
Vancomycin - pharmacology
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Summary:Many potent antibiotics fail to treat bacterial infections due to emergence of drug-resistant strains. This surge of antimicrobial resistance (AMR) calls in for the development of alternative strategies and methods for the development of drugs with restored bactericidal activities. In this context, we surmised that identifying aptamers using nucleotides connected to antibiotics will lead to chemically modified aptameric species capable of restoring the original binding activity of the drugs and hence produce active antibiotic species that could be used to combat AMR. Here, we report the synthesis of a modified nucleoside triphosphate equipped with a vancomycin moiety on the nucleobase. We demonstrate that this nucleotide analogue is suitable for polymerase-mediated synthesis of modified DNA and, importantly, highlight its compatibility with the SELEX methodology. These results pave the way for bacterial-SELEX for the identification of vancomycin-modified aptamers.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27248927