A Bis‐Zn²⁺‐Pyridyl‐Salen‐Type Complex Conjugated to the ATP Aptamer: An ATPase‐Mimicking Nucleoapzyme

Abstract

Catalytic nucleic acids consisting of a bis‐Zn2+‐pyridyl‐salen‐type ([di‐ZnII 3,5 bis(pyridinylimino) benzoic acid]) complex conjugated to the ATP aptamer act as ATPase‐mimicking catalysts (nucleoapzymes). Direct linking of the Zn2+ complex to the 3′‐ or 5′‐end of the aptamer (nucleoapzymes I and II) or its conjugation to the 3′‐ or 5′‐end of the aptamer through bis‐thymidine spacers (nucleoapzymes III and IV) provided a set of nucleoapzymes exhibiting variable catalytic activities. Whereas the separated bis‐Zn2+‐pyridyl‐salen‐type catalyst and the ATP aptamer do not show any noticeable catalytic activity, the 3′‐catalyst‐modified nucleoapzyme (nucleoapzyme IV) and, specifically, the nucleoapzyme consisting of the catalyst linked to the 3′‐position through the spacer (nucleoapzyme III) reveal enhanced catalytic features in relation to the analogous nucleoapzyme substituted at the 5′‐position (kcat=4.37 and 6.88 min−1, respectively). Evaluation of the binding properties of ATP to the different nucleoapzyme and complementary molecular dynamics simulations suggest that the distance separating the active site from the substrate linked to the aptamer binding site controls the catalytic activities of the different nucleoapzymes.

Aptamer-Modified Cu2+-Functionalized C-Dots: Versatile Means to Improve Nanozyme Activities-“Aptananozymes”

“…Molecular dynamic simulations were applied to elucidate the structure–function relationships within the catalyst-aptamer conjugates to account for the variable catalytic activities of the nucleoapzyme structures. Different nucleoapzymes catalyzing the oxidation of dopamine or N -hydroxy- l -arginine by H 2 O 2 to yield aminochrome or citruline, respectively, 40 the hydrolysis of ATP to ADP by mimicking ATPase, 42 and the oxygenation of aryl C–H bonds of l -tyrosinamide to yield its catechol derivatives 43 have been demonstrated. In principle, this concept can be applied to develop libraries of aptamer-nanozyme hybrids of variable catalytic activities by the conjugation of the 3′ or 5′ end of the aptamer to the nanozyme, the introduction of spacer units that modulate the flexibility of the aptamers in respect to the heterogeneous nanozyme, and by further engineering the DNA bridging modules linking the aptamers to the nanozymes, for example, by introducing stimuli-responsive bridging units.…”

Aptamer-Functionalized Hybrid Nanostructures for Sensing, Drug Delivery, Catalysis and Mechanical Applications

“…The second example for constructing nucleoapzymes includes the modification of the aptamer with a transition metal complex as catalytic unit. This is introduced by describing a set of nucleoapzymes mimicking the catalytic activity of ATPase; the hydrolysis of ATP to ADP [177]. A set of nucleoapzymes consisting of the ATP aptamer modified with the bis-Zn 2+ pyridyl-salene complex was synthesized, (Figure 14).…”

Review of Zinc(II) Scaffolds: Efficient Role in Gene Delivery

“…Especially, the Zncyclen-HD exhibited better serum-tolerance than the polyethylenimine (PEI). [36] Based on their experimental results, they have found that di-Zn(II)-3,5-bis(pyridinylimino) benzoic acid hybrid with ATP-aptamer mimics the catalytic property of ATPase enzyme. Y. Tabata et al has reported three-pullulan based derivatives, i. e., pullulan-triethylenetetramine (Ti), pullulandiethylenetriamine pentaacetic acid (DTPA) and pullulanspermine [37] for the gene-expression only in the liver cells.…”

“…Willner and co‐workers have reported that the transfection efficiency of bis‐Zn(II)‐pyridyl‐Salen‐type complex 9 (Figure ) was dramatically increased when it was coordinated to cyclen‐based poly‐cationic ATP‐aptamer. Especially, the Zn‐cyclen‐HD exhibited better serum‐tolerance than the polyethylenimine (PEI) . Based on their experimental results, they have found that di‐Zn(II)‐3,5‐bis(pyridinylimino) benzoic acid hybrid with ATP‐aptamer mimics the catalytic property of ATPase enzyme.…”