Target Self‐Enhanced Selectivity in Metal‐Specific DNAzymes

Abstract

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.

Recent Advances on DNAzyme‐Based Sensing

“…In considering of the crucial role of nucleotides adjacent to the cleavage junction, a few chemical modifications have also been made to assist metal ions binding and improve the selectivity of DNAzymes. In 2020, the Liu group reported a modified DNAzymes named MGL−Zn03 by introducing a glycyl‐histidine‐functionalized tertiary amine ligand within the cleavage junction through solid‐phase synthesis(Figure 2A) [29] . The discovered MGL−Zn03 could specifically bind with three Zn 2+ ions to increase the selectivity over Co 2+ by ∼5000‐fold.…”

“… Schematic illustration of chemical modification of DNAzymes. (A) The library design for in vitro selection with Zn 2+ ions and chemical structures of the normal rAG junction and the modified rA G junction [29] . Copyright 2019, Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim.…”

Modular Design of G-Quadruplex MetalloDNAzymes for Catalytic C–C Bond Formations with Switchable Enantioselectivity

“…Interestingly, with respect to htelL S 3 B, changing the position of T 18 and L S19 in loop 3 to L S18 and T 19 led to an inversion of the enantioselectivity in htelL S 3 C (57% ee (S)), while changing the position of L S17 and T 18 to L S18 and T 17 as in htelL S 3 D had only a minor influence on the enantioselectivity (91% ee (R)). More drastic was the effect when L S was incorporated twice in loop 1 and once in loop 3 (htelL S 3 A, htelL S 3 E, and htelL S 3 F), leading to poor conversions (<30%) and enantioselectivities (<31% ee).…”

“…As a solution, chelate ligands were bound to DNA via covalent or non-covalent interactions. In this way, peroxidase-like reactions and Zn II - and Ce IV -dependent site-specific RNA and DNA cleavage were established. − Roelfes and Feringa pioneered the design of Cu II complexes that bind to double-stranded DNA for enantio­selective transformations such as Diels–Alder reactions, Michael additions, and Friedel–Crafts reactions. − In recent times, also DNA G-quadruplexes were discovered for chiral catalysis, and a first example was reported in 2010 by Moses et al They showcased an enantio­selective Diels–Alder reaction by planar Cu II chelates, non-covalently stacked on a terminal G-quartet . Later, Wang and Li demonstrated Friedel–Crafts reactions, cyclopropanations, and other transformations.…”

On-site detection of fish furunculosis by combining DNAzyme and carboxyl-functionalized graphene

“…DNAzyme can specifically recognize metal ions, small molecules and proteins, such as Pb 2+ (Liang et al, 2016), Cu 2+ (Chen et al, 2016), Uo 2 2+ (Manochehry et al, 2018), histidine (He et al, 2015), lipopolysaccharide (Miao et al, 2018), glucose (Yang et al, 2015) and so on. DNAzymes are characterized by low cost, high sensitivity, strong compatibility, and ability to undergo modifications easily (Liu et al, 2017;Mcghee et al, 2017;Peng et al, 2018;Huang et al, 2020). DNAzymes are used as molecular recognition elements, and fluorescence or color change is used as a characterization signal (Cao et al, 2019).…”