1. Enzymatic Synthesis of Vancomycin-Modified DNA
- Author
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Chiara Figazzolo, Frédéric Bonhomme, Saidbakhrom Saidjalolov, Mélanie Ethève-Quelquejeu, Marcel Hollenstein, Chimie bioorganique des acides nucléiques - Bioorganic chemistry of nucleic acids, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Learning Planet Institute [Paris] (LPI), Chimie biologique épigénétique - Epigenetic Chemical Biology (EpiCBio), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), C.F. gratefully acknowledges the Pasteur-Paris University (PPU) International Ph.D. Program that has received funding from INCEPTION Project (PIA/ANR-16-CONV-0005), the 'Ecole Doctorale Frontières de l’Innovation en Recherche et Education—Programme Bettencourt' for financial support. The authors gratefully acknowledge financial support from Institut Pasteur., and ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016)
- Subjects
Oligonucleotides ,Pharmaceutical Science ,[CHIM.THER]Chemical Sciences/Medicinal Chemistry ,DNA-Directed DNA Polymerase ,Analytical Chemistry ,DNA polymerases ,Vancomycin ,Drug Discovery ,Modified nucleic acids DNA polymerases Nucleoside triphosphates Primer extension reactions SELEX antimicrobial resistance ,[CHIM]Chemical Sciences ,antimicrobial resistance ,Physical and Theoretical Chemistry ,SELEX ,[CHIM.ORGA]Chemical Sciences/Organic chemistry ,Nucleotides ,Organic Chemistry ,Modified nucleic acids ,SELEX Aptamer Technique ,DNA ,Aptamers, Nucleotide ,Anti-Bacterial Agents ,modified nucleic acids ,nucleoside triphosphates ,primer extension reactions ,Chemistry (miscellaneous) ,Molecular Medicine ,Primer extension reactions ,Nucleoside triphosphates - Abstract
International audience; 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.
- Published
- 2022
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