Self-Assembling Catalysts for Selective Nucleic Acid Modification

Understanding and controlling the biology of nucleic acids is partially a challenge in synthetic chemistry: How to precisely manipulate a single subunit in an ocean of near-identical units. Addressing this challenge in chemo- and site-selectivity is vital since tinkering with a molecules structure offers one of the best ways to learn how it works. Tinkering also offers a pathway to refine and even create new function. Evolution is exactly this sort of iterative variation to craft function. Accordingly, exploring and expanding the role of a particular DNA or RNA would be facilitated by synthetic access variants consisting of diverse structural perturbations. This task is especially urgent for RNA since every year new layers in its rich chemistry and biology are unveiled. Enzymes are Nature's solution to whole host of selectivity issues including functional group compatibility, chemoselectivity, and site-selectivity. Their outstanding selectivity stems not only from the primary active-site interactions that promote catalysis, but also from the secondary interactions that guide substrate selection and binding. Drawing inspiration from Nature's two-pronged approach, we will identify catalysts for the modification of nucleic acids and then append these catalysts to guiding sequences that precisely define the sites of alkylataion through Watson-Crick base-pairing. New chemical methods to selectively modify nucleic acids are important because of their central role in biology and medicine.