DNA enzymes

Santoro SW, Joyce GF (1997) A general purpose RNA-cleaving DNA enzyme, Proc Natl Acad Sd USA 94 4262-4266... 

Note THF = tetrahydrofuran BHT = butylated hydroxytoluene, an antioxidant Camptothecin (CM) = causes inhibition of the DNA enzyme topoisomerase (Top 1) which induces DNA damage and apoptosis DHT = dihydrotestosterone PrEC = normal prostate stromal cells LNCaP, PC-3, DU-145 = neoplastic prostate epithelial cells (See Table 21.1). 

Pun SH, Tack F, Bellocq NC, Cheng J, Grubbs BH, Jensen GS, Davis ME, Brewster M, Janicot M, Janssens B, Floren W, Bakker A (2004) Targeted delivery of RNA-cleaving DNA enzyme (DNAzyme) to tumor tissue by transferrin-modified, cyclodextrin-based particles. Cancer Biol Ther 3 641-650... 

The following sections describe some of the more common procedures of preparing DNA-enzyme conjugates. 

This is also true for a number of in vitro selected DNA enzymes which were selected under divalent metal-free buffer conditions [59,60]. These results contradict the common assumption that all ribozymes are metalloenzymes and provide a number of ribozymes for which it will be very interesting to determine their exact catalytic mechanisms at high resolution. 

Presumably, the L-histidine cofactor is loosely bound to the DNA-enzyme which positions its imidazole group to serve as a general base catalyst. The histidine/DNA complex thus works by a mechanism that is similar to the first... 

Mectianism of Action A fluoroquinolone that inhibits the DNA enzyme gyrase in susceptible microorganisms, interfering with bacterial cell replication and repair Tfier-apeuticEffect Bactericidal. 

Figure 12-28 (A) A hairpin ribozyme formed from the minus strand of a satellite RNA associated with tobacco ringspot virus. On the basis of hydroxyl radical footprinting (see Fig. 5-50), to identify protected areas a folding pattern that brings domains A and B together to form a compact catalytic core has been proposed.798 (B) A "leadzyme," a ribozyme dependent upon Pb2+ for cleavage of RNA.802 803 (C) An RNA-cleaving DNA enzyme.804...

It is a commonly held belief that RNA preceded DNA in the early evolution of living systems. If this is the case then the first DNA polymerases must have been capable of transferring sequence information from RNA to DNA. Enzymes of this sort are called reverse transcriptases because they do the reverse of common transcriptases (see chapter 28). Reverse transcriptases no longer play the central role in genetic information transfer, but they are still found in all species and function in a number of capacities in both cellular and viral metabolism. 

Ordoukhanian, P., Joyce, G.F. RNA-cleaving DNA enzymes with altered regio- or enan-tioselectivity. J. Am. Chem. Soc. 124, 12499-12506 (2002). 

Deoxyribozymes (also called DNA enzymes or DNAzymes) are specific sequences of DNA that have catalytic activity. All currently known deoxyribozymes have been identified by in vitro selection from large random-sequence DNA pools (Joyce, 2004 Silverman, 2009). The catalytic range of DNA encompasses both oligonucleotide and nonoligonucleotide substrates (Baum and Silverman, 2008 Silverman, 2008). This report focuses on deoxyribozymes that are useful for reactions of RNA substrates, especially to assist studies of RNA structure, folding, and catalysis. 

The selection strategies and outcomes for identifying branch-forming deoxyribozymes have been described in part elsewhere (Silverman, 2008). Here, the most useful DNA enzymes are briefly described. First, the Mg2+-dependent 7S11 deoxyribozyme creates 2/,5/-branched RNA with a... 

Extracellular barriers (DNA, enzymes, mucus) Paucity of receptors Proteosome-mediated degradation Inhibition of second-strand synthesis Airway clearance, anti-inflammatory, anti-protease pre-treatments Alternate serotypes, targeted capsid mutants Proteosome inhibitors (tripeptides, anthracyclines) Tyrosine kinase inhibitors... 

---