Deoxyribozymes: DNA catalysts for bioorganic chemistry

Silverman, Scott

doi:10.1039/b411910j

Cited by 125 publications

(71 citation statements)

References 43 publications

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“…In this context, the nucleic acids RNA and DNA show a great potential far from their natural function as an origin/vector of genetic information. Once discovered as a feature of RNA, catalytic (ribozymes [87], e.g., RNA polymerases [88]) and regulatory activities (riboswitches) [98,90] are engineered for RNA as well as DNA (DNAzymes [91], RNase [92], peroxidase [93], photolyase [94]) for the purposes of the synthetic biology [95,96]. Rational networks made of nucleic acids are used to program [97], calculate [98], and store [99] events of molecular interactions and facilitate regulatory circuits, e.g., for the adaption of a system.…”

Section: Droplet-based Reaction Systemsmentioning

confidence: 99%

Biotechnology and Bioprocess Engineering – From the First Ullmann's Article to Recent Trends

et al. 2015

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For several thousand years, biotechnology and its associated technical processes have had a great impact on the development of mankind. Based on empirical methods, in particular for the production of foodstuffs and daily commodities, these disciplines have become one of the most innovative future issues. Due to the increasing detailed understanding of cellular processes, production strains can now be optimized. In combination with modern bioprocesses, a variety of bulk and fine chemicals as well as pharmaceuticals can be produced efficiently. In this article, some of the current trends in biotechnology are discussed.

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Section: Droplet-based Reaction Systemsmentioning

confidence: 99%

Biotechnology and Bioprocess Engineering – From the First Ullmann's Article to Recent Trends

et al. 2015

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“…Indeed, many in vitro selection studies have focused on the identification of DNA motifs that cut RNA phosphodiester linkages, mainly because RNA-cleaving catalysts are especially interesting from an applications viewpoint (see below). [6,9] The first deoxyribozyme ever described, in 1994, was a lead-dependent catalyst capable of cleaving a single RNA phosphodiester linkage embedded in a DNA molecule. [12] In the following years, further searches led to the identification of deoxyribozymes that cleave RNA phosphodiester bonds in the presence of Mg 2 + or Ca 2 + [13][14][15][16][17][18][19] or even in the absence of divalent metal ions.…”

Section: Known Catalytic Dnas Come From In Vitro Selectionmentioning

confidence: 99%

“…[3][4][5][6][7][8][9] In vitro selection is an approach that mimics natural selection in a chemical setting. [10,11] It exploits the creation of large libraries of DNA sequences, together with the possibility of amplifying a tiny subset of selected molecules through the polymerase chain reaction (PCR).…”

Section: Known Catalytic Dnas Come From In Vitro Selectionmentioning

confidence: 99%

“…The technique has several limits: for example, during selection the allowed reaction time cannot usually be shortened below a few seconds; furthermore, selected catalysts are optimized for single-turnover (rather than multiple-turnover) performance. [9] One limit that might be even more relevant, however, is the practical difficulty in selecting catalytic DNAs of large size.…”

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DNA Catalysis: Potential, Limitations, Open Questions

Peracchi

2005

ChemBioChem

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“…If this can be established, then we anticipate that the DNA constraint approach will be useful for studying RNA structure-function relationships that involve catalysis and not only folding. Here, we report the identification of a new deoxyribozyme [5] for attachment of DNA to RNA, which considerably aids the synthetic procedure. Using this deoxyribozyme, we describe the successful application of DNA constraints to control the catalytic activity of the hammerhead ribozyme.…”

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confidence: 98%

Allosteric Control of Ribozyme Catalysis by Using DNA Constraints

Zelin

Silverman

2007

ChemBioChem

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[a] Covalent, crosslinking tethers have previously been attached to nucleic acids for control of structure and catalysis.[1] Surprising results have been found, such as a study with the Tetrahymena group I intron ribozyme in which crosslinks that should substantially disrupt structure nevertheless did not suppress catalysis nearly as much as expected. [2] As an alternative approach to control macromolecular structure, we recently described the use of covalently attached DNA strands as constraints on RNA conformation.[3] When two complementary DNA strands are attached to a large and foldable RNA, DNA duplex formation can compete with native RNA structure. This can destabilize RNA folding (by > 6 kcal mol À1 in one instance)because the DNA duplex must be disrupted in order for the RNA to fold properly. The integrity of the DNA constraint can be modulated by added enzymes, oligonucleotides, or smallmolecule ligands that cleave or interact with the DNA strands. [4] These studies suggested the possibility that the catalytic activity of a ribozyme, and not merely the structure of a foldable RNA, could be controlled by strategic attachment of DNA strands. If this can be established, then we anticipate that the DNA constraint approach will be useful for studying RNA structure-function relationships that involve catalysis and not only folding. Here, we report the identification of a new deoxyribozyme [5] for attachment of DNA to RNA, which considerably aids the synthetic procedure. Using this deoxyribozyme, we describe the successful application of DNA constraints to control the catalytic activity of the hammerhead ribozyme. We provide initial data that allow us to understand the structural basis of catalytic control in terms of modulation of tertiary structure but not secondary structure.To facilitate synthetic access to DNA-derivatized RNA, which previously required a laborious procedure that depended on assembly of numerous RNA fragments, [3] we used in vitro selection to identify new deoxyribozymes that ligate DNA to RNA. We previously reported the 7S11 deoxyribozyme, [6] which ligates an RNA 2'-hydroxyl group to a 5'-triphosphorylated or 5'-adenylated [7] RNA (Figure 1 A). Although 7S11 and an improved variant, 10DM24, [8] show modest activity when 5'-adenylated DNA is used in place of analogous RNA, the ligation yield was impractically low when examined with an RNA substrate that differed from the arbitrary sequence used during the original selection procedure (data not shown). Therefore, we performed a new selection experiment directly with 5'-adenylated DNA.[9]With a branch-site adenosine that provided the 2'-hydroxyl group in the RNA substrate, we iterated selection rounds (50 mm CHES, pH 9.0, 40 mm MgCl 2 , 150 mm NaCl, and 2 mm KCl at 37 8C) using an incubation time as low as merely 1 min in the later rounds. The pool activity was 34 % at round 9, after which individual deoxyribozymes were cloned and characterized. One of these deoxyribozymes, 9FQ4 (Figure 1 B), was examined further. Deoxyribozyme 9FQ4 had...

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Deoxyribozymes: DNA catalysts for bioorganic chemistry

Cited by 125 publications

References 43 publications

Biotechnology and Bioprocess Engineering – From the First Ullmann's Article to Recent Trends

Biotechnology and Bioprocess Engineering – From the First Ullmann's Article to Recent Trends

DNA Catalysis: Potential, Limitations, Open Questions

Allosteric Control of Ribozyme Catalysis by Using DNA Constraints

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