Bridging the gap between proteins and nucleic acids: A metal-independent RNAseA mimic with two protein-like functionalities

Two synthetically modified nucleoside triphosphate analogues (adenosine mod ified with an imidazole and uridine modified with a cationic amine) are enz ymatically polymerized in tandem along a degenerate DNA library for the com binatorial selection of an RNAse A mimic. The selected activity is consiste nt with both electrostatic and general acid/base catalysis at physiological pH in the absence of divalent metal cations. The simultaneous use of two m odified nucleotides to enrich the catalytic repertoire of DNA-based catalys ts has never before been demonstrated and evidence of general acid/base cat alysis at pH 7.4 for a DNAzyme has never been previously observed in the ab sence of a divalent metal cation or added cofactor, This work illustrates h ow the incorporation of protein-like functionalities in nucleic acids can b ridge the gap between proteins and oligonucleotides underscoring the potent ial for using nucleic acid scaffolds in the development of new materials an d improved catalysts for use in chemistry and medicine.