Center Researchers create New Tool in the Field of DNA/RNA Mimetics (February 2016)

Nucleic acids such as DNA and RNA serve multiple esssential roles in all living organisms. DNA is the blueprint that dictates the composition and sequence of all proteins that give form and function to our cells. It also plays a role in the frequency of production of those same proteins. RNA carries the instructions from DNA to the cellular machinery responsible for the assembly of proteins. RNA, like DNA, determines, in part, how often particular proteins are expressed. The versatility of nucleic acids lies in its base-pair binding specificity, wherein oligomeric polymers of a particular sequence will bind and interact only with oligomers of complimentary sequence.

Because of their primacy in many biological roles and because of their high selectivity for intermolecular interactions, nucleic acids have captured the interest and imagination of researchers both within and outside of biological sciences. But whether in a biological context or not, working with native nucleic acids presents many challenges. For example, almost all living things have evolved to protect their own genomes from foreign nucleic acid contamination. Thus, ubiquitous enzymes known generally as "nucleases", break apart the phosphodiester backbone that comprises the backbone of both DNA and RNA. In addition, the negatively charged polymer backbone of nucleic acids also causes electrostatic repulsion which limits the strength of the binding of complimentary polymers as well as the solubility in less polar organic solvents. This causes real challenges in applying DNA to materials design outside the realm of aqueous, biological systems.

Researchers at in the Center have developed a new nucleic acid analog by replacing the phosphodiester backbone with thioether backbones using high-efficiency thiol-click reactions. Chris Bowman and coworkers have demonstrated the synthesis of a variety of nucleobase-containing monomers to take advantage of both radically and anionically mediated polymerization mechanisms.

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With these monomers, the team generated DNA-analogous oligomers with periodic nucleobase sequence motifs that exhibited sequence-specific binding. These oligomers, bound to multifunctional polymers, self-assembled into dynamic organogel materials, portending the application of this new technology for diverse materials such as tissue engineered cell-seeded scaffolds and self-healing materials.

Unlike DNA, these new CNA or "Click Nucleic Acids" are not subject to nuclease degradation nor do they require high salt concentrations to shield a charged backbone. Moreover, the efficiency of the reactions used to generate the polymers allows economically feasible scalability for applications where the high cost of DNA would otherwise be prohibitive.

This work was published in W. Xi, S. Pattanayak, C. Wang, B. Fairbanks, T. Gong, J. Wagner, C. J. Kloxin, and C. N. Bowman, " Clickable Nucleic Acids: Sequence-Controlled Periodic Copolymer/Oligomer Synthesis by Orthogonal Thiol-X Reactions," Angewandte Chemie Int. Ed. 54 (48), 14462-14467 (2015).


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