Metal Ion‐Terpyridine‐Functionalized L‐Tyrosinamide Aptamers: Nucleoapzymes for Oxygen Insertion into CH Bonds and the Transformation of L‐Tyrosinamide into Amidodopachrome

Luo, Guo‐Feng; Biniuri, Yonatan; Vázquez‐González, Margarita; Wulf, Verena; Fadeev, Michael; Lavi, Ronit; Willner, Itamar

doi:10.1002/adfm.201901484

Cited by 13 publications

(17 citation statements)

References 39 publications

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“…[4][5][6][7] G-quadruplex (G4)-DNAzymes represent a particular class of DNAzymes in which a four-stranded G4-DNA interacts with the cofactor hemin to perform hemoenzyme-type reactions. [8][9][10][11][12] The current popularity of G4-DNAzymes stems from the versatile designability [13][14][15][16][17] and excellent biocompatibility of G4 precatalysts. [18][19][20][21] Unfortunately, the performances of G4-DNAzymes are still below those of corresponding enzymes, leading to new research and strategies for improved performance.…”

Section: Introductionmentioning

confidence: 99%

A Push–Pull Mechanism Helps Design Highly Competent G-Quadruplex-DNA Catalysts

et al. 2021

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Massive efforts are currently being invested to improve the performance, versatility, and scope of applications of nucleic acid catalysts. G-quadruplex (G4)/hemin DNAzymes are of particular interest owing to their structural programmability and chemical robustness. However, optimized catalytic efficiency is still bottleneck and the activation mechanism is unclear. Herein, we have designed a series of parallel G4s with different proximal cytosine (dC) derivatives to fine-tune the hemin-binding pocket for G4-DNAzymes. Combining theoretical and experimental methods, we have assessed the dependence of catalytic enhancement on the electronic properties of proximal dCs and demonstrated how proximal dCs activate catalytic proficiency. These results provide interesting clues in recapitulating the push-pull mechanism as the basis of peroxidase activity and help to devise a new strategy to design highly competent DNA catalysts whose performances are of the same order as protease.

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Section: Introductionmentioning

confidence: 99%

A Push–Pull Mechanism Helps Design Highly Competent G-Quadruplex-DNA Catalysts

et al. 2021

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“…We designed the nucleoapzymes by extending the sequence of PW17 with that of the full or partial sequence of L-tyrosinamide-binding aptamer (TamBA): the full TamBA sequence (49 nucleotides; see Supporting Table S1) was placed either on the 3' or the 5'-end of PW17 (Figure 2A); the partial sequences were used in a split-aptamer approach, where the two parts of the TamBA sequences were placed on either side of the PW17 sequence (Figure 2B). [21] These nucleoapzyme constructs were tested for their ability to catalyze the conjugation of L-tyrosinamide (1) and NML (2). Importantly, TamBA itself did not increase the activity of hemin (Figure 2C, Supporting Table S4).…”

Section: Resultsmentioning

confidence: 99%

Aptamer‐Assisted Bioconjugation of Tyrosine Derivatives with hemin/G‐quadruplex (hGQ) DNAzyme Nucleoapzyme Nanostructures

et al. 2021

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Hemin/G-quadruplex (hGQ) DNAzymes are horseradish peroxidase-mimicking catalysts capable of the oxidation of a variety of substrates. We now implement aptamer-functionalized hGQ DNAzymes, also known as nucleoapzymes, to achieve increased bioconjugation of N-methyl luminol to tyrosinecontaining residues and peptides. We found that the presence of a tyrosinamide-binding aptamer leads to a 12-fold increase in the catalytic rate constant (k cat ), and the saturation kinetics curves that were obtained provide evidence for the involve-ment of the substrate binding site in the reaction. The application of the best performing nucleoapzymes for the modification of Tyr-containing peptides reveals that (i) the aptamer also recognizes the ligand structure when this is embedded in a larger peptide structure, and (ii) distant residues in the peptide substrate can influence the conversion. As such, we show that nucleoapzymes display enzyme-like features and provide an additional tool in the toolbox of bioconjugation chemistry.

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“…In addition, the Fe(III)–terpyridine complex linked to the tyrosinamide aptamer was found to act as a nucleoapzyme that catalyzes the oxidation of tyrosinamide ( 3 ) to amidodopachrome ( 5 ) by H 2 O 2 ( Figure 4 A). 39 This oxygen-insertion process occurred only in the presence of an ascorbic acid/H 2 O 2 mixture. A set of Fe(III)–terpyridine-functionalized tyrosinamide aptamers, in which the catalytic site was attached directly to the 5′- and 3′-ends of the aptamer (configurations I and II, respectively) or through 4T bridging tethers (configurations III and IV), were assembled.…”

Section: Metal–ligand Complex-functionalized Aptamers As Nucleoapzymesmentioning

confidence: 99%

Mimicking Functions of Native Enzymes or Photosynthetic Reaction Centers by Nucleoapzymes and Photonucleoapzymes

et al. 2020

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The covalent linkage of catalytic units to aptamer sequence-specific nucleic acids exhibiting selective binding affinities for substrates leads to functional scaffolds mimicking native enzymes, nucleoapzymes. The binding of the substrates to the aptamer and their structural orientation with respect to the catalytic units duplicate the functions of the active center of enzymes. The possibility of linking the catalytic sites directly, or through spacer units, to the 5′-end, 3′-end, and middle positions of the aptamers allows the design of nucleoapzyme libraries, revealing structure–functions diversities, and these can be modeled by molecular dynamics simulations. Catalytic sites integrated into nucleoapzymes include DNAzymes, transition metal complexes, and organic ligands. Catalytic transformations driven by nucleoapzymes are exemplified by the oxidation of dopamine or l -arginine, hydroxylation of tyrosine to l -DOPA, hydrolysis of ATP, and cholic acid-modified esters. The covalent linkage of photosensitizers to the tyrosinamide aptamer leads to a photonucleoapzyme scaffold that binds the N -methyl- N ′-(3-aminopropane)-4,4′-bipyridinium-functionalized tyrosinamide to the aptamer. By linking the photosensitizer directly, or through a spacer bridge to the 5′-end or 3′-end of the aptamer, we demonstrate a library of supramolecular photosensitizer/electron acceptor photonucleoapzymes mimicking the functions of photosystem I in the photosynthetic apparatus. The photonucleoapzymes catalyze the photoinduced generation of NADPH, in the presence of ferredoxin-NADP + -reductase (FNR), or the photoinduced H 2 evolution catalyzed by Pt nanoparticles. The future prospects of nucleoapzymes and photonucleoapzymes are discussed.

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Metal Ion‐Terpyridine‐Functionalized L‐Tyrosinamide Aptamers: Nucleoapzymes for Oxygen Insertion into CH Bonds and the Transformation of L‐Tyrosinamide into Amidodopachrome

Cited by 13 publications

References 39 publications

A Push–Pull Mechanism Helps Design Highly Competent G-Quadruplex-DNA Catalysts

A Push–Pull Mechanism Helps Design Highly Competent G-Quadruplex-DNA Catalysts

Aptamer‐Assisted Bioconjugation of Tyrosine Derivatives with hemin/G‐quadruplex (hGQ) DNAzyme Nucleoapzyme Nanostructures

Mimicking Functions of Native Enzymes or Photosynthetic Reaction Centers by Nucleoapzymes and Photonucleoapzymes

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