Evaluating the Catalytic Potential of a General RNA‐Cleaving FANA Enzyme. (6th December 2019)

• Record Type: Journal Article
• Authors: Wang, Yajun; Vorperian, Alexander; Shehabat, Mouhamad; Chaput, John C.
• Is Part Of: Chembiochem. Volume 21:Number 7(2020)
• Page Start: 1001
• Page End: 1006
• Publication Date: 2019-12-06
• Subjects: DNAzymes -- FANA -- FANAzymes -- xenonucleic acids -- XNA; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201900596
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: The discovery of synthetic genetic polymers (XNAs) with catalytic activity demonstrates that natural genetic polymers are not unique in their ability to function as enzymes. However, all known examples of in vitro selected XNA enzymes function with lower activity than their natural counterparts, suggesting that XNAs might be limited in their ability to fold into structures with high catalytic activity. To explore this problem, we evaluated the catalytic potential of FANAzyme 12–7, an RNA‐cleaving catalyst composed entirely of 2′‐fluoroarabino nucleic acid (FANA) that was evolved to cleave RNA at a specific phosphodiester bond located between an unpaired guanine and a paired uracil in the substrate recognition arm. Here, we show that this activity extends to chimeric DNA substrates that contain a central riboguanosine (riboG) residue at the cleavage site. Surprisingly, FANAzyme 12–7 rivals known DNAzymes that were previously evolved to cleave chimeric DNA substrates under physiological conditions. These data provide convincing evidence that FANAzyme 12–7 maintains the catalytic potential of equivalent DNAzymes, which has important implications for the evolution of XNA catalysts and their contributions to future applications in synthetic biology. Abstract : Activity FANAtic : Evaluation of the catalytic potential of xenonucleic acid catalysts (XNAzyme) reveals that 2'‐fluoroarabino nucleic acid enzymes (FANAzymes) rival their DNA counterparts at cleaving a chimeric DNA substrate under simulated physiological conditions. This finding has important implications for future applications in synthetic biology and medicine.