関: catalytic DNA、DNAzyme

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/27 14:49:17」(JST)

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Deoxyribozymes or DNA enzymes or catalytic DNA, or DNAzymes are DNA molecules that have the ability to perform a chemical reaction, such as catalytic action.^[1] In contrast to the RNA ribozymes, which have many catalytic capabilities, in nature DNA is only associated with gene replication and nothing else. The reasons are that DNA lacks the 2'-hydroxyl group of RNA, which diminishes its chemical reactivity and its ability to form complex tertiary structures, and that nearly all biological DNA exists in the double helix conformation in which potential catalytic sites are shielded.^{[citation needed]} In comparison to proteins built up from 20 different monomers both RNA and DNA have a much more restricted set of monomers (4) to choose from which limits the construction of interesting catalytic sites. For these reasons DNAzymes exist only in the laboratory.

Discovery[edit source | edit]

The first deoxyribozyme was discovered in 1994 ^[2] by current Yale Professor Ronald R. Breaker while a postdoctoral fellow in the laboratory of Prof. Gerald Joyce at The Scripps Research Institute in La Jolla, CA. This deoxyribozyme assists in lead ion dependent RNA cleaving operations. Catalytic amplification was found to be 100-fold compared to the uncatalysed reaction. Many other deoxyribozymes have since been developed that catalyse DNA phosphorylation, DNA adenylation, DNA deglycosylation, porphyrin metalation, thymine dimer photoreversion and DNA cleavage. Of particular interest are DNA ligases.^[3] These molecules have demonstrated remarkable chemoselectivity in RNA branching reactions. Although each repeating unit in a RNA strand owns a free hydroxyl group, the DNA ligase takes just one of them as a branching starting point. An accomplishment unattainable with traditional organic chemistry. DNAzymes have found practical use in metal biosensors.^[4]

For example, the DNA molecule 5'-GGAGAACGCGAGGCAAGGCTGGGAGAAATGTGGATCACGATT-3' which acts as a deoxyribozyme that uses light to repair a thymine dimer, using serotonin as cofactor^[5] .^[6]

Usage[edit source | edit]

With the aid of combinatorial chemistry techniques a great many DNA sequences (up to 10¹⁶ of them) can be generated in a single experiment with 20 to 200 base pairs each, that can be screened for a specific catalytic task. In this way the sheer number of DNA candidates make up for DNA being more appropriate for information storage than for catalysis. An inherent disadvantage of DNA enzymes is product inhibition and single-turnover behavior. It may therefore be argued if DNA enzymes can be counted as true catalysts. On the other hand low catalytic turnover is observed with many natural (non-DNA) occurring enzymes. Although the discovery of RNA enzymes predates that of DNA enzymes the latter have some distinct advantages. DNA has better cost-effectiveness and DNA can be made with longer sequence length and can be made with higher purity in Solid-phase synthesis.

Chirality is another property that a DNAzyme can exploit. DNA occurs in nature as a right-handed double helix and in asymmetric synthesis a chiral catalyst is a valuable tool in the synthesis of chiral molecules from an achiral source. In one application an artificial DNA catalyst was prepared by attaching a copper ion to it through a spacer.^[7] The copper - DNA complex catalysed a Diels-Alder reaction in water between cyclopentadiene and an aza chalcone. The reaction products (endo and exo) were found to be present in an enantiomeric excess of 50%. Later it was found that an enantiomeric excess of 99% could be induced, and that both the rate and the enantioselectivity were related to the DNA sequence.

Other uses of DNA in chemistry are in DNA-templated synthesis, Enantioselective catalysis,^[8] DNA nanowires and DNA computing.^[9]

References[edit source | edit]

^ Breaker, Ronald R. (May 1997). "DNA enzymes". Nature Biotechnology (PDF|format= requires |url= (help)) 15: 427–431. PMID 9131619. |accessdate= requires |url= (help)
^ Breaker RR,; Joyce GF. (December 1994). "A DNA enzyme that cleaves RNA". Chem Biol. 1 (4): 223–9. doi:10.1016/1074-5521(94)90014-0. PMID 9383394.
^ Scott K. Silverman (2004). "Deoxyribozymes: DNA catalysts for bioorganic chemistry" (PDF). Org. Biomol. Chem. 2 (19): 2701–06. doi:10.1039/B411910J. PMID 15455136.
^ Juewen Liu; Yi Lu (2004). "Optimization of a Pb²⁺-Directed Gold Nanoparticle/DNAzyme Assembly and Its Application as a Colorimetric Biosensor for Pb²⁺". Chem. Mater. 16 (17): 3231–38. doi:10.1021/cm049453j.
^ Daniel J.-F. Chinnapen; Dipankar Sen (Jan 6 2004). "A deoxyribozyme that harnesses light to repair thymine dimers in DNA.". US National Library of Medicine: Proceedings of the National Academy of Sciences of the United States of America.
^ Daniel J.-F. Chinnapen; Dipankar Sen (Jan 6 2004). "A deoxyribozyme that harnesses light to repair thymine dimers in DNA". Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences of the United States of AmericaEdited by Gerald F. Joyce, The Scripps Research Institute, La Jolla, CA, and approved November 10, 2003 (received for review September 15, 2003)
^ Gerard Roelfes; Ben L. Feringa (2005). "DNA-Based Asymmetric Catalysis". Angewandte Chemie International Edition 44 (21): 3230–2. doi:10.1002/anie.200500298. PMID 15844122. ^{[dead link]}
^ García-Fernández, Almudena; Roelfez, Gerard (2012). "Chapter 9. Enantioselective catalysis at the DNA Scaffold". In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel. Interplay between Metal Ions and Nucleic Acids. Metal Ions in Life Sciences 10. Springer. pp. 249–268. doi:10.1007/978-94-007-2172-2_9.
^ Yoshihiro Ito; Eiichiro Fukusaki (2004). "DNA as a ‘Nanomaterial’" (PDF). Journal of Molecular Catalysis B: Enzymatic 28 (4-6): 155–166. doi:10.1016/j.molcatb.2004.01.016.

External links[edit source | edit]

Deoxyribozyme at the US National Library of Medicine Medical Subject Headings (MeSH)

English Journal

Enhanced DNA sensing via catalytic aggregation of gold nanoparticles.

Huttanus HM, Graugnard E, Yurke B, Knowlton WB, Kuang W, Hughes WL, Lee J.SourceDepartment of Materials Science & Engineering, Boise State University, Boise, ID 83725, United States.
Biosensors & bioelectronics.Biosens Bioelectron.2013 Dec 15;50:382-6. doi: 10.1016/j.bios.2013.06.063. Epub 2013 Jul 11.
A catalytic colorimetric detection scheme that incorporates a DNA-based hybridization chain reaction into gold nanoparticles was designed and tested. While direct aggregation forms an inter-particle linkage from only one target DNA strand, catalytic aggregation forms multiple linkages from a single
PMID 23891867

Amperometric aptasensor for thrombin detection using enzyme-mediated direct electrochemistry and DNA-based signal amplification strategy.

Bai L, Chai Y, Yuan R, Yuan Y, Xie S, Jiang L.SourceEducation Ministry Key Laboratory on Luminescence and Real-Time Analysis, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, People's Republic of China.
Biosensors & bioelectronics.Biosens Bioelectron.2013 Dec 15;50:325-30. doi: 10.1016/j.bios.2013.06.050. Epub 2013 Jul 4.
In this work, a new electrochemical aptasensor based on direct electron transfer and electrocatalysis of horseradish peroxidase (HRP) using exonuclease-catalyzed target recycling and hybridization chain reaction (HCR) for signal amplification was developed for highly sensitive detection of thrombin.
PMID 23880107

Conformational switch for cisplatin with hemin/G-quadruplex DNAzyme supersandwich structure.

Wang G, He X, Chen L, Zhu Y, Zhang X, Wang L.SourceKey Laboratory of Chem-Biosensing, Anhui Province, Anhui Normal University, Wuhu 241000, PR China; Key Laboratory of Functional Molecular Solids, Anhui Province, Anhui Normal University, Wuhu 241000, PR China; College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241000, PR China.
Biosensors & bioelectronics.Biosens Bioelectron.2013 Dec 15;50:210-6. doi: 10.1016/j.bios.2013.06.046. Epub 2013 Jun 29.
Cisplatin is a representative of cytotoxic and antineoplastic metallodrugs used for the treatment of various malignancies. In this paper, an enzyme-free amplification platform involving an autonomous target triggered process that yields the formation of the hemin/G-quadruplex DNAzyme wires was desig
PMID 23859921

Japanese Journal

In vitro selection, characterization, and application of deoxyribozyme that cleave RNA

SILVERMAN SK.
Nucleic Acid Res 33, 6151-6163, 2005
NAID 30018412862

2E09-1 デオキシリボザイムを用いた新規なrRNA定量法の開発(環境浄化・修復・保全技術,一般講演)

末永光,白政優子,金川貴博
日本生物工学会大会講演要旨集平成16年度, 165, 2004-08-25
NAID 110007321018

A deoxyribozyme-based molecular automaton

STOJANOVIC MN
Nat Biotechnol 21, 1069-1074, 2003
NAID 80016117953

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