Cell-free nucleic acids

Two types of change are possible at C-7, epimerisation and modification of the substituent. Of the compounds tested to date, the 7,9-diepimer of 3-demethoxy-daunomydn is the compound most closely related to 7-epiadriamycin. This 7,9-diepimer stabilises the DNA helix to melting to a lesser degree than with dauno-mydn and consequently it is a less active inhibitor of cell-free nucleic acid synthesis than daunomycin [211]. It is impossible to conclude whether this is due to inversion of configuration at C-7 or at C-9 or at both centres. The only other compounds for which data are available are the 2 epimers of the simplified analogue discussed earlier, compound (71). Both epimers of (71) show equiv-... 

While most cells do not take up naked DNA in the absence of the physical or chemical treatments described above, muscle cells appear to be an exception. Direct injection of free nucleic acids in saline solutions into skeletal and cardiac muscles has been shown to result in prolonged expression (Wolff et al, 1991 Kitsis et al, 1991). By using this method, the 12 kilobase human dystrophin gene, defective in muscular dystrophy patients, has been introduced into the muscle cells of mice (Partridge, 1991 Ascadi et al, 1991). 

Copper is an essential trace element. It is required in the diet because it is the metal cofactor for a variety of enzymes (see Table 50—5). Copper accepts and donates electrons and is involved in reactions involving dismu-tation, hydroxylation, and oxygenation. However, excess copper can cause problems because it can oxidize proteins and hpids, bind to nucleic acids, and enhance the production of free radicals. It is thus important to have mechanisms that will maintain the amount of copper in the body within normal hmits. The body of the normal adult contains about 100 mg of copper, located mostly in bone, liver, kidney, and muscle. The daily intake of copper is about 2—A mg, with about 50% being absorbed in the stomach and upper small intestine and the remainder excreted in the feces. Copper is carried to the liver bound to albumin, taken up by liver cells, and part of it is excreted in the bile. Copper also leaves the liver attached to ceruloplasmin, which is synthesized in that organ. 

Decreased cerebral blood flow, resulting from acute arterial occlusion, reduces oxygen and glucose delivery to brain tissue with subsequent lactic acid production, blood-brain barrier breakdown, inflammation, sodium and calcium pump dysfunction, glutamate release, intracellular calcium influx, free-radical generation, and finally membrane and nucleic acid breakdown and cell death. The degree of cerebral blood flow reduction following arterial occlusion is not uniform. Tissue at the... 

Subsequently, similar experiments were done with viral nucleic acids. The pure viral nucleic acid, when added to cells, led to the synthesis of complete virus particles the protein coat was not required. This process is called transfection. More recently, DNA has been used in cell-free extracts to program the synthesis of RNA that functions as the template for the synthesis of proteins characteristic of the DNA... 

Free radical attack on cells can be directed on many biological molecules including lipids, proteins, and nucleic acids. Several studies suggested that proteins could be the most vulner-... 

The pH value in a solid tumor is typically 0.2-0.5 units lower than in normal tissues. Therefore it may be possible to design pH-depen-dent cell-selective antitumor agents. Some free radicals are known to damage biological targets and especially to cleave nucleic acids (233). Alkylcobalt(III) complexes such as 53 generate alkyl radicals via ho-... 

He, M. and Taussig, M.J., Single step generation of protein arrays from DNA by cell-free expression and in situ immobilization (PISA method). Nucleic Acid Res., 29(15), 1-6, 2001. 

A. Salvage pathways allow synthesis of nucleotides from free purines or pyrimidines that arise from nucleic acid degradation or dietary sources, which is more economical for the cell than de novo synthesis. 

The free purine released can then be used in the biosynthesis of new nucleic acids within the cell. 

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