Deoxyribozymes: Catalytically Active DNA Molecules

Schlosser, Kenny; McManus, Simon A.; Li, Yingfu

doi:10.1002/3527608192.ch10

Cited by 5 publications

(3 citation statements)

References 69 publications

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“…Metal and nucleic acid interaction has been a fascinating field of study with potential for advancement of both basic coordination chemistry and structural biology, and practical biotechnological and pharmaceutical applications. − This field became even more exciting when RNA , and then DNA were discovered in the early 1980s and 1990s, respectively, to possess catalytic or enzymatic functions, supported by metal ion cofactors. The catalytic RNA, often called ribozymes, occur naturally, whereas catalytic DNA (often called deoxyribozymes or DNAzymes) have not yet been isolated in nature, and they are obtained in the laboratory by a combinatorial biology technique called in vitro selection. − …”

Section: Introductionmentioning

confidence: 99%

Activity, Folding and Z-DNA Formation of the 8-17 DNAzyme in the Presence of Monovalent Ions

et al. 2009

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The effect of monovalent ions on both the reactivity and global folding of the 8–17 DNAzyme is investigated and the results are compared with the hammerhead ribozyme, which has similar size and secondary structure. In contrast to the hammerhead ribozyme, the 8–17 DNAzyme activity is not detectable in the presence of 4 M K+, Rb+, and Cs+ and the complex, [Co(NH3)6]3+. Only Li+, NH4+ and to a lesser extent Na+ showed detectable activity. The observed rate constants (kobs ~10−3 min−1 for Li+ and NH4+) are ~1000-fold lower than that in the presence of 10 mM Mg2+, and ~200,000-fold slower than the estimated rate in the presence of 100 µM Pb2+. Since the hammerhead ribozyme displays monovalent ion-dependent activity that is often within ~10-fold of divalent metal ion-dependent activity, these results suggest that the 8–17 DNAzyme, obtained by in vitro selections has evolved to have a more stringent divalent metal ion requirement for high activity as compared to the naturally occurring ribozymes, making the 8–17 DNAzyme an excellent choice as a Pb2+ sensor with high selectivity. In contrast to the activity data, folding was observed in the presence of all the monovalent ions investigated, although those monovalent ions that do not support DNAzyme activity have weaker binding affinity (Kd ~0.35 M for Rb+ and Cs+), while those that confer DNAzyme activity possess stronger affinity (Kd ~0.22 M for Li+, Na+ and NH4 +). In addition, a correlation between metal ion charge density, binding affinity and enzyme activity was found among mono- and divalent metal ions except Pb2+; higher charge density resulted in stronger affinity and higher activity, suggesting that the observed folding and activity is at least partially due to electrostatic interactions between ions and the DNAzyme. Finally, circular dichroism (CD) study has revealed Z-DNA formation with the monovalent metal ions, Zn2+ and Mg2+; the Kd values obtained using CD were in the same range as those obtained from folding studies using FRET. However, Z-DNA formation was not observed with Pb2+. These results indicate that Pb2+-dependent function follows a different mechanism from the monovalent metal ions and other divalent metal ions; in the presence of latter metal ions, metal-ion dependent folding and structural changes, including formation of Z-DNA, play an important role in the catalytic function of the 8–17 DNAzyme.

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Section: Introductionmentioning

confidence: 99%

Activity, Folding and Z-DNA Formation of the 8-17 DNAzyme in the Presence of Monovalent Ions

et al. 2009

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“…In the presence of Pb 2+ , the enzyme cleaves the substrate into two pieces (Figure B). The same DNAzyme motif (known as the 8-17 DNAzyme) has been independently selected under a variety of conditions by several research groups using different metal ions. , In a comprehensive study performed by Li and co-workers, the reason for the recurrence of this particular DNAzyme was attributed to its high catalytic rate, capability to cleave many dinucleotide junctions, small catalytic core, and high tolerance to nucleotide mutations . To incorporate nanoparticle binding functions, the substrate was extended on both ends (Figure C).…”

Section: Directed Assembly In Response To a Single Internal Stimulusmentioning

confidence: 99%

Smart Nanomaterials Inspired by Biology: Dynamic Assembly of Error-Free Nanomaterials in Response to Multiple Chemical and Biological Stimuli

2007

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Three-dimensional functional nanoscale assembly requires not only self-assembly of individual nanomaterials responsive to external stimuli, such as temperature, light, and concentrations, but also directed assembly of many different nanomaterials in one-pot responsive to multiple internal stimuli signaling the needs for such materials at a specific location and a particular time. The use of functional DNA (DNAzymes, aptamers, and aptazymes) to meet these challenges is reviewed. In addition, a biology-inspired proof-reading and error correction method is introduced to cope with errors in nanomaterials assembly.

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“…Very recently, Willner demonstrated that an aptamer-linked DNAzyme showed enhanced catalysis compared with the free DNAzyme. 13b , 14 Furthermore, the rate of reaction correlated with the binding affinity of the aptamer for its target, strongly suggesting that aptamers could be used as recognition domains in site-selective reagents and that selecting and/or designing binding and catalytic function separately can result in effective rate enhancement. 15 …”

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confidence: 99%

A DNA-conjugated small molecule catalyst enzyme mimic for site-selective ester hydrolysis

et al. 2018

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Deoxyribozymes: Catalytically Active DNA Molecules

Cited by 5 publications

References 69 publications

Activity, Folding and Z-DNA Formation of the 8-17 DNAzyme in the Presence of Monovalent Ions

Activity, Folding and Z-DNA Formation of the 8-17 DNAzyme in the Presence of Monovalent Ions

Smart Nanomaterials Inspired by Biology: Dynamic Assembly of Error-Free Nanomaterials in Response to Multiple Chemical and Biological Stimuli

A DNA-conjugated small molecule catalyst enzyme mimic for site-selective ester hydrolysis

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