RNA Cleavage by a DNA Enzyme with Extended Chemical Functionality

Santoro, Stephen W.; Joyce, Gerald F.; Sakthivel, Kandasamy; Gramatikova, Svetlana; Cf, Barbas

doi:10.1021/ja993688s

Cited by 350 publications

(262 citation statements)

References 38 publications

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“…To date, no naturally occurring DNAzymes have been identified, and all known DNAzymes have been isolated with a combinatorial biology method called in vitro selection in the laboratory (28)(29)(30)(31)(32). Most DNAzymes require metal ion cofactors for structure and function, and many DNAzymes show high metal-binding affinity and specificity (33)(34)(35)(36)(37)(38). For example, the 8-17 DNAzyme can be activated by a trace amount of Pb 2ϩ (39), and it has been transformed into sensors for Pb 2ϩ (39)(40)(41)(42).…”

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confidence: 99%

A catalytic beacon sensor for uranium with parts-per-trillion sensitivity and millionfold selectivity

Liu

Brown

Meng

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

488

476

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Here, we report a catalytic beacon sensor for uranyl (UO 2 2؉ ) based on an in vitro-selected UO 2 2؉ -specific DNAzyme. The sensor consists of a DNA enzyme strand with a 3 quencher and a DNA substrate with a ribonucleotide adenosine (rA) in the middle and a fluorophore and a quencher at the 5 and 3 ends, respectively. The presence of UO 2 2؉ causes catalytic cleavage of the DNA substrate strand at the rA position and release of the fluorophore and thus dramatic increase of fluorescence intensity. The sensor has a detection limit of 11 parts per trillion (45 pM), a dynamic range up to 400 nM, and selectivity of >1-million-fold over other metal ions. The most interfering metal ion, Th(IV), interacts with the fluorescein fluorophore, causing slightly enhanced fluorescence intensity, with an apparent dissociation constant of Ϸ230 M. This sensor rivals the most sensitive analytical instruments for uranium detection, and its application in detecting uranium in contaminated soil samples is also demonstrated. This work shows that simple, cost-effective, and portable metal sensors can be obtained with similar sensitivity and selectivity as much more expensive and sophisticated analytical instruments. Such a sensor will play an important role in environmental remediation of radionuclides such as uranium.DNA ͉ DNAzyme ͉ fluorescence ͉ deoxyribozyme ͉ catalytic DNA

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confidence: 99%

A catalytic beacon sensor for uranium with parts-per-trillion sensitivity and millionfold selectivity

Liu

Brown

Meng

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

488

476

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“…In vitro selection is a combinatorial technique that generates receptors, ligands, and catalysts from nucleic acid libraries containing as many as 10 14 -10 16 different molecules and is a powerful method to explore the sequence space of biopolymers in search of functional domains. Some effort has been devoted to developing in vitro selection processes that use modified monomer triphosphates as substrates for polymerases (27)(28)(29)(30)(31)(32)(33)(34)(35)(36), and several in vitro selection experiments have been undertaken to select for catalysts or aptamers whose functions depend on the presence of modified nucleotides (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48), with notable success (39,40,(43)(44)(45)(46)(47). On the other hand, modified building blocks have not proven to always be critical in obtaining superior receptors or catalysts (40,42,48,49).…”

mentioning

confidence: 99%

“…For example, comparable or better Diels-Alderase ribozymes were obtained from pools assembled with natural nucleotides (49) vs corresponding modified pools (41). Similarly, no significant catalytic advantage for modified DNA is evident when phosphodiesterase activity was the selection criterion for sequences containing imidazole-modified deoxyuridine in the presence of divalent zinc, relative to sequences constructed of natural deoxynucleotides in the presence of either divalent magnesium (37,50) or divalent zinc (51).…”

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confidence: 99%

A Novel, Modification-Dependent ATP-Binding Aptamer Selected from an RNA Library Incorporating a Cationic Functionality

et al. 2003

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An analogue of uridine triphosphate containing a cationic functional group was incorporated into a degenerate RNA library by enzymatic polymerization. In vitro selection experiments using this library yielded a novel receptor that binds ATP under physiological pH and salt conditions in a manner completely dependent on the presence of the cationic functionality. The consensus sequence and a secondary structure model for the ATP binding site were obtained by the analysis of functional sequences selected from a partially randomized pool based on the minimal parental sequence. Mutational studies of this receptor indicated that several of the modified uridines are critical for ATP binding. Analysis of the binding of ATP analogues revealed that the modified RNA receptor makes numerous contacts with ATP, including interactions with the triphosphate group. In contrast, the aptamer repeatedly isolated from natural RNA libraries does not interact with the triphosphate group of ATP. The incorporation of a cationic amine into nucleic acids clearly allows novel interactions to occur during the molecular recognition of ligands, which carries interesting implications for the RNA world hypothesis. In addition, new materials generated from such functionalized nucleic acids could be useful tools in research and diagnostics.

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“…Imidazole (Im), and their derivatives are ubiquitous in biological and biochemical structure and function [2,3]. Im derivatives have also found wide applications in drug design in the forms of antitumor and anticancer agents [4,5].…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of 3,6-bis(imidazol-1-yl)pyridazine, C10H8N6

Jin¹,

Zheng²,

Wang³

et al. 2010

Zeitschrift Für Kristallographie - New Crystal Structures

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Source of materialThe title compound was synthesized according to the published procedure [1]. 3,6-bis(imidazol-1-yl)pyridazine (21 mg, 0.10 mmol) was then dissolved in 8mLof85%formic acid, The solution was then filtered into atest tube and left standing at room temperature. After about one month colorless needle-like crystals were obtained. X-ray diffraction analysis indicated that the title compound crystallizes without solvent molecules. Experimental detailsHydrogen atoms attached to the Ca toms were placed in calculated positions with d(C-H) =0.93 Å.All U iso values were restrained on U eq values of the parent atoms. DiscussionImidazole (Im), and their derivatives are ubiquitous in biological and biochemical structure and function [2,3]. Im derivatives have also found wide applications in drug design in the forms of antitumor and anticancer agents [4,5]. In addition to the above mentioned fields, imidazole derivatives can also be used in building coordination polymeric frameworks [6,7]. In the title crystal structure all of the bond distances and angles are in the normal range. The two imidazole rings are situated at trans configuration ( figure, top). The imidazole rings and the pyridazine ring are planar with the largest deviation from the least square plane of 0.0061 Å.T he dihedral angle between the imidazole ring and the pyridazine rings are 7.4°and 1.5°,respectively, the dihedral angle between the two imidazole rings in the same molecule is 6.4°,which is different to the published results [8]. Each two molecules are connected through two C-H···Nhy-drogen bonds to form adimer. The adjacent dimers are connected by two 3,6-bis(imidazol-1-yl)pyridazines along [001] through eight C-H···Nhydrogen bonds (figure, bottom). Every terminal Natom of the imidazole group form two C-H···Nhydrogen bonds with the dimers in bifurcate mode with the C-Nd istances of 3.460 Å and 3.482 Å,respectively. Caused by such weak interactions, the compound displayed corrugated layer structure. These layers were further stacked along [100] through C-H···Nhydro-gen bonds and p-p interactions (with centroid-centroid distance of 3.374 Å)toform 3D network structure.

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RNA Cleavage by a DNA Enzyme with Extended Chemical Functionality

Cited by 350 publications

References 38 publications

A catalytic beacon sensor for uranium with parts-per-trillion sensitivity and millionfold selectivity

A catalytic beacon sensor for uranium with parts-per-trillion sensitivity and millionfold selectivity

A Novel, Modification-Dependent ATP-Binding Aptamer Selected from an RNA Library Incorporating a Cationic Functionality

Crystal structure of 3,6-bis(imidazol-1-yl)pyridazine, C10H8N6

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