Artificial metal-base pairs have become increasingly important in nucleic acids chemistry due to their high thermal stability, water solubility, orthogonality to natural base pairs and low cost of production. These interesting properties combined with ease of chemical and enzymatic synthesis have prompted their use in several practical applications including the construction of nanomolecular devices, ions sensors and metal nanowires. Chemical synthesis of metal base pairs is highly efficient and enables the rapid screening of novel metal base pair candidates. However, chemical synthesis is limited to rather short oligonucleotides and requires rather important synthetic efforts. Herein, we discuss recent progress made for the enzymatic construction of metal base pairs which can alleviate some of these limitations. First, we highlight the possibility of generating metal base pairs using canonical nucleotides and then describe how modified nucleotides can be used in this context. We also provide a description of the main analytical techniques used for the analysis of the nature and the formation of metal-base pairs together with relevant examples of their applications.
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.
Methods for the real-time monitoring of the substrate acceptance of modified nucleotides by DNA polymerases are in high demand. In a step towards this aim, we have incorporated ferrocene-based abasic...
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