Enzymatic construction of metal-mediated nucleic acid base pairs

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 that 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.