Nucleic acid modification

Fig. 1 Chemical structures of backbone modifications used in therapeutic nucleic acid analogs. Shown are the unmodified DNA/RNA chemical structures in addition to a selection of first (PS), second (OMe, MOE), and third generation (PNA, LNA, MF) nucleic acid modifications...

There are a number of various commercial products designed for DNA/ RNA extraction, but their use may lead to variable results. Based on the evidence that formalin-induced modification of protein is similar to that of nucleic acid modification by formalin (Fig. 3.1),15-19 our research group at the University of Southern California has conducted a serial study of AR based heating protocols for DNA/RNA extraction from FFPE tissues following our experience of the AR principle as applied to IHC on tissue sections heating under the influence of pH.19-21... 

In addition to stabilizing appendages, dynamic nucleic acid modification has been applied in supramolecular chemistry to develop novel materials. To this end, Lehn and coworkers developed dynamic nucleic acid analogs,... 

It has been proposed that 8-aminodcoxyguanosinc is formed from the nitronate tautomer of 2-nitropropane either by base nitrosation followed by reduction, or via an enzyme-mediated conversion of the nitronate anion to hydroxyiam ine-O-sulfonate or acetate, which yields the highly reactive nitrenium ion NHj (Sodum et al., 1993). Sodum et al. (1994) have provided evidence for the activation of 2-nitropropane to an aminating species by rat liver aryl sulfotransferase in vitro and in vivo. Pretreatment of rats with the aryl sulfotransferase inhibitors pentachlorophenol or 2,6-dichloro-4-nitrophenol significantly decreased the levels of nucleic acid modifications produced in the liver by 2-nitropropane treatment. Partially purified rat liver aryl sulfotransferase activated 2-nitropropane and its nitronate at neutral pH to a reactive species that aminated guanosine at the position. This activation was dependent on the presence of the enzyme, its specific cofactor adenosine 3 -phosphate 5 -phosphosulfate, and mercaptoethanol. It was inhibited... 

Adsorption is the simplest method to immobilize nucleic acids on surfaces. The method does not require special reagents or nucleic acid modifications. Materials reported for this type of immobilization include nitrocellulose, nylon membranes, polystyrene, metal oxide surfaces (palladium or aluminum oxide), or carbon transducers. 

The development of assay techniques that have convenience of solid-phase hybridization and are rapid and sensitive will have a significant impact on diagnostics and genomics [3]. In this respect, SPE genosensors have several advantages they are safe because they are disposable, they are reproducible, they are inexpensive, and the overall procedure is quite fast. In this respect, electrochemical adsorption (adsorption controlled by a positive potential) is an easy to perform and rapid way of immobilization. The method does not require special reagents or nucleic acid modifications. 

Recall that oxidative stress results from reactive oxygen or nitrogen species that are not fully neutralized by anti-oxidants (see Chapter 24). The increase in reactive oxygen and nitrogen species results in protein, lipid, and nucleic acid modifications. Many neurodegenerative diseases, such as Alzheimer disease, Parkinson disease, and Lou Gehrig disease, have in common increased oxidative stress. 

D. P. Hornby, High throughput analysis of nucleic acid modification reactions using IP RP HPLC, Amd. Biochem. 301, 290, 2002. 

Torigoe, H. et al, 2Co,4 -C-methylene bridged nucleic acid modification promotes pyrimidine motif triplex DNA formation at physiological pH thermodynamic and kinetic studies, /. Biol. Chem., 276, 2354, 2001. 

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