4.8 Article

Target Self-Enhanced Selectivity in Metal-Specific DNAzymes

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 9, Pages 3573-3577

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201915675

Keywords

aptamers; biosensors; DNAzymes; metal ions; SELEX

Funding

  1. Natural Sciences and Engineering Research Council of Canada (NSERC)
  2. Global Water Futures project of the Canada First Research Excellence Fund (CFREF)

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Highly selective recognition of metal ions by rational ligand design is challenging, and simple metal binding by biological ligands is often obscured by nonspecific interactions. In this work, binding-triggered catalysis is used and metal selectivity is greatly increased by increasing the number of metal ions involved, as exemplified in a series of in vitro selected RNA-cleaving DNAzymes. The cleavage junction is modified with a glycyl-histidine-functionalized tertiary amine moiety to provide multiple potential metal coordination sites. DNAzymes that bind 1, 2, and 3 Zn2+ ions, increased their selectivity for Zn2+ over Co2+ ions from approximately 20-, 1000-, to 5000-fold, respectively. This study offers important insights into metal recognition by combining rational ligand design and combinatorial selection, and it provides a set of new DNAzymes with excellent selectivity for Zn2+ ions.

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