Evaluating the Catalytic Potential of a General RNA-Cleaving FANA Enzyme.


Journal

Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360

Informations de publication

Date de publication:
01 04 2020
Historique:
received: 25 09 2019
revised: 31 10 2019
pubmed: 5 11 2019
medline: 18 5 2021
entrez: 5 11 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31680396
doi: 10.1002/cbic.201900596
doi:

Substances chimiques

2'-deoxy-2'-fluoro-beta-D-arabinonucleic acid 0
Arabinonucleotides 0
DNA, Catalytic 0
Polymers 0
RNA 63231-63-0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1001-1006

Informations de copyright

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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Auteurs

Yajun Wang (Y)

Departments of Pharmaceutical Sciences, Chemistry, and Molecular Biology and Biochemistry, University of California, Irvine, 101 Theory, Suite 100, Irvine, CA, 92697-3958, USA.

Alexander Vorperian (A)

Departments of Pharmaceutical Sciences, Chemistry, and Molecular Biology and Biochemistry, University of California, Irvine, 101 Theory, Suite 100, Irvine, CA, 92697-3958, USA.

Mouhamad Shehabat (M)

Departments of Pharmaceutical Sciences, Chemistry, and Molecular Biology and Biochemistry, University of California, Irvine, 101 Theory, Suite 100, Irvine, CA, 92697-3958, USA.

John C Chaput (JC)

Departments of Pharmaceutical Sciences, Chemistry, and Molecular Biology and Biochemistry, University of California, Irvine, 101 Theory, Suite 100, Irvine, CA, 92697-3958, USA.

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