Enzymatic Synthesis of Vancomycin-Modified DNA

Area of Science:

• Biochemistry
• Molecular Biology
• Drug Discovery

Background:

• Antimicrobial resistance (AMR) is a growing threat, rendering many antibiotics ineffective against bacterial infections.
• Novel strategies are crucial for developing drugs with restored bactericidal activities to combat AMR.

Purpose of the Study:

• To synthesize a novel nucleotide analogue incorporating a vancomycin moiety for potential use in developing new antimicrobial agents.
• To explore the utility of this modified nucleotide in creating aptamers capable of restoring antibiotic efficacy.

Main Methods:

• Synthesis of a nucleoside triphosphate modified with vancomycin on the nucleobase.
• Demonstration of polymerase-mediated synthesis of modified DNA using the novel nucleotide.
• Assessment of the nucleotide's compatibility with the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) methodology.

Main Results:

• Successful synthesis of a vancomycin-modified nucleoside triphosphate.
• Confirmation that the modified nucleotide is suitable for polymerase-driven DNA synthesis.
• Demonstration of the nucleotide's compatibility with the SELEX process, enabling aptamer selection.

Conclusions:

• The developed vancomycin-modified nucleotide is a promising tool for generating chemically modified aptamers.
• This approach facilitates bacterial-SELEX for identifying aptamers that can combat antimicrobial resistance.
• This research opens new avenues for developing effective treatments against drug-resistant bacterial infections.