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. In contrast to the RNA ribozymes, which have many catalytic capabilities, in nature DNA is thought to be associated only with gene replication. 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. 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 probably exist only in the laboratory.
The first deoxyribozyme was discovered in 1994  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. 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.
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. 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.
- Breaker, Ronald R. (May 1997). "DNA enzymes". Nature Biotechnology (PDF ) 15: 427–431. doi:10.1038/nbt0597-427. PMID 9131619.
- 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.