Catalytic DNAs

While indirect selections work quite well for antibodies they have been less successful in the case of catalytic nucleic acids. There are only three examples which prove that it is possible in principle to obtain a ribo- or deoxyribozyme by selecting an aptamer that binds to a TSA A rotamase ribozyme [7], a ribozyme capable of catalyzing the metallation of a porphyrin derivative [92], and one catalytic DNA of the same function [93]. Another study reported the selection of a population of RNA-aptamers which bind to a TSA for a Diels-Alder reaction but the subsequent screen for catalytic activity was negative for all individual RNAs tested [94]. The attempt to isolate a transesterase ribozyme using the indirect approach also failed [95]. 

The only indirect selection that led to a catalytic DNA is a deoxyribozyme that catalyzes the same class of porphyrin metallation as the aforementioned ribozyme. The ssDNA oligonucleotide showed a k at of 13 h" for the insertion of into mesoporphyrin IX [93, 96-99]. This corresponds to a rate enhancement of 1400 compared to the uncatalyzed reaction which is as good as a catalytic antibody for the same reaction. 

A new dimension in the development of nucleic acid based catalysts was introduced by Breaker and Joyce in 1994 when they isolated the first deoxyribozyme [111]. It is not unexpected that DNA is also able to catalyze chemical reactions because it was shown previously that ssDNA aptamers which bind to a variety of ligands can be isolated by in vitro selection [141]. In the meantime, several deoxyribozymes have been described which expand the range of chemical transformations accelerated by nucleic acid catalysts even further and raising question whether even catalytic DNA might have played some role in the pre-biotic evolution of hfe on earth [69-71]. 

Fig. 13. The deoxyribozyme bottom strand) hybridizes to the RNA substrate oligonucleotide top strand). The site of cleavage is indicated by the arrow (R = A or G Y = U or C). The sequences of the helical parts of the enzyme can be chosen as desired, so that almost any RNA sequence can be targeted by the catalytic DNA...

Fig. 14. Sequences and secondary structures of one of the selected L-histidine-dependent catalytic DNAs...

Silverman, S. K. (2008). Catalytic DNA (deoxyribozymes) for synthetic applications-current abilities and future prospects. Chem. Commun. (Camb.) 14(30), 3467—3485. 

Ribozymes involve which of the following a antisense deoxynucleotides b protein-RNA combination c catalytic RNA d catalytic DNA e mitochondrial DNA. 

Lu Y, Liu J, Li J, Bruesehoff PJ, Pavot CM-B, Brown AK. New highly sensitive and selective catalytic DNA biosensor for metal ions. Biosens Bioelectron 2003 18 529 10. 

Tack, F., Bakker, A., Maes, S., Dekeyser, N., Braining, M., Elissen-Roman, C., Janicot, M., Brewster, M. et al. (2006) Modified polypropylene inline) dendrimers as effective transfection agents for catalytic DNA enzymes (DNAzymes). Journal of Drug Targeting 14 69-86. 

Alessio Peracchi obtained a degree in veterinary medicine from the University of Parma in 1989, and later a Ph.D. in molecular biotechnology at the Catholic University of the Sacred Heart, Piacenza, Italy in 1994, and conducted postdoctoral research at Stanford University. In 1998, he became a permanent researcher at the University of Parma, and since 2000 he is an associate professor of biochemistry at the same institution. In 2001, he was nominated EMBO Young Investigator by the European Molecular Biology Organization. His research centers on the function and evolution of catalytic biomacromolecules, contributing to the field with studies on protein enzymes, ribozymes, and deoxyribozymes (catalytic DNAs). 

Finally, it is important to recognize that folded oligonucleotides can also be functional. For example, Sen s group has described a series of DNA oligonucleotide aptamers that are catalysts. Aptamers, selected with a transition state analog A-methylmesoporphyrin, catalyzed the Cu and Zn metallation of porphyrins. This catalytic DNA, which requires for its... 

Catalytic DNA is made possible because single-stranded DNA can adopt complex tertiary structures in a similar way to RNA, although unlike RNA no DNA-based catalysts have yet been found in nature. Both DNA aptamers and DNA catalysts (deoxyribozymes) can be... 

Bruesehoff P. J., Li J., Augustine A. J., and Lu Y., Improving metal ion specificity during in vitro selection of catalytic DNA, Comb. Chem. High. Throughput. Screening., 5, 327-335, 2002. 

Figure 4.5 General operation mode of DNA machines exemplified by the catalytic scission of a substrate DNA strand. In the absence of the fuel-analyte molecule (blue), the DNA machine is inactive (1). Binding of the fuel and subsequent hybridization start the machine s operations (2), in this case a catalytical DNA cleavage reaction (3). Release of waste products due to reduced base pairing resets the machine to its starting configuration (1) and begins the next round of action. Note that different examples of machines performing a vast array of actions other than DNA cutting are shown. (See insert for color representation.)...

Nucleic acids Ribozymes (catalytic RNA) and deoxyribozymes (catalytic DNA)... 

Some nucleic acids are capable of self-splicing. These catalytic DNA and RNA are known as deoxyribozymes (Li and Breaker, 1999 Sheppard et al, 2000) and ribozymes (Doherty and Doudna, 2000 Scott and Klug, 1996) respectively. The 3 - and/or 2 -hydroxyls of DNA/RNA serve as a catalytic site that invariably requires a metal ion for the catalytic activity. Deoxyribozymes are quasi-catalytic while ribozymes can be catalytic, e.g. ribonuclease P (RNase P) as well as quasi-catalytic, e.g. introns and hammerhead RNAs. RNase P resources are maintained at http //www.mbio.ncsu.edu/RnaseP/homeJitml... 

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