Intercalation with nucleic acids

The dye 4, 6-Diamidino-2-PhenyIindole (DAPI) in 0.001%W/V aqueous solution can be used directly on smears, ciyosections and embedded specimens to locate and count culture bacteria, without regard to their viability, in cheese and other cultured products. The dye reacts with nucleic acids by intercalation. Excitation at 360nm is best for this dye. It is worth noting two other facts about its use. DAPI cross reacts with dairy proteins, but the color of the protein-dye complex is different from that of the nucleic acid-dye complex (the latter is a steely blue/white) and so the two reactions may be discriminated. The dye also may take up to 15 minutes to enter bacterial cells, particularly spores, before fluorescence is observed. An alternative nucleic acid dye, Ethidium Bromide, has less contrast between the fluorescence induced in cells and the fluorescence of cross-reacting dairy proteins. It should be tried in other products such as meats if DAPI is not successful. 

From various physical and biophysical properties of nucleic acid analogs the most important property for the present purpose is their interaction with nucleic acids. The spectrophotometric methods for detection of complex formation were applied to all combinations of polyvinyl polynucleotide analogs and natural polynucleotides (Fig. 3). In aqueous media hypochromic complexes were formed in combinations where the bases in the polynucleotide and analog were complementary. Poly-l-vinylcytosine is soluble in aqueous-propylene glycol base-pair type complexes were detected there also. An analog of polyinosinate, poly-9-vinylhypoxanthine, is soluble only in solutions of a detergent, sodium dodecylsulfate. This detergent intercalates into the polymer and conveys to it an... 

Anthracydines have several modes of action leading to anticancer activity. They intercalate between base pairs in DNA, interfering with nucleic acid synthesis. Anthracydines also inhibit DNA topoisomerases I and II, which leads to DNA double-strand breaks. In addition, doxorubicin and daunorubicin may form complexes with metals such as iron. Although these metal-anthracycline complexes result in oxygen free radical formation, which may contribute to antitumor activity, membrane damage incurred from the free radicals is thought to be the mechanism responsible for... 

The interaction of biologically active molecules like dyes with nucleic acids is of great interest because such molecules are used as drugs in chemotherapy (e.g. antibiotics, antitumor substances) other ones can induce mutations and tumors. They form intermolecular complexes with nucleic acids. A special class are dyes interacting with DNA by intercalation. These dye molecules are inserted between two base pairs (Fig. 10). A peculiarity of such complexes are base-sequence-dependent effects, for example, the fluorescence behaviour or the energy transfer inside the complex. These processes can depend on the type of base pairs between which the dye molecules are inserted. The quantum yield of fluorescence for some dyes after intercalation is much higher in AT-AT than in AT-GC or GC-GC sequences. 

Tris(phenanthroline) complexes of ruthenium(II), cobalt(III), and rhodium(III) are octahedral, substitutionally inert complexes, and as a result of this coordina-tive saturation the complexes bind to double-helical DNA through a mixture of noncovalent interactions. Tris(phenanthroline) metal complexes bind to the double helix both by intercalation in the major groove and through hydrophobic association in the minor groove. " " Intercalation and minor groove-binding are, in fact, the two most common modes of noncovalent association of small molecules with nucleic acids. In addition, as with other small molecules, a nonspecific electrostatic interaction between the cationic complexes and the DNA polyanion serves to stabilize association. Overall binding of the tris(phenanthroline) complexes to DNA is moderate (log K = 4)." ... 

Many recents studies have focused on applications of metallointerca-lation, which is also an important noncovalent interaction of metal complexes with nucleic acids. Intercalation is a common mode of association of small molecules with DNA, where a flat aromatic heterocyclic moiety inserts and stacks in between the DNA base pairs (13). Lippard and coworkers (14) determined in 1974 that platinum(II) complexes containing an aromatic heterocyclic ligand such as terpyridine could intercalate in DNA. Figure 2c shows such a stacking interaction of such a complex in a dinucleotide (15). Recently, we have found that intercalation is not restricted to completely flat, square planar complexes, but partial intercalation of ligands coordinated to octahedral metal centers is feasible as well... 

To understand the unique swelling behavior of DNA cryogels in EtBr solutions, one has to consider the nature of interactions of EtBr with nucleic acids in aqueous solutions. Previous studies indicate the existence of two main types of EtBr binding to DNA [121, 122]. At low values of r, EtBr binds strongly to DNA sites by intercalation, which appears to be saturated when one EtBr molecule is bound for every 2.1 0.2 base pairs, i.e., r = 0.24 0.02. This is the accepted maximum... 

Quinacrine concentrates in the scolex of the parasite and causes the muscles needed for holding onto the intestinal wall to relax. The worms are stained yellow and pass from the body, still aUve. Quinacrine can intercalate with DNA and inhibit nucleic acid synthesis. It creates fluorescent bands in deoxyadenylate—deoxythmidylate-rich regions of DNA and has been used as a stain in the study of human genetics. 

The most commonly used dye in fluorescence studies on nucleic acids is ethidium bromide. The dye has broad excitation bands centered around 280 and 460 nm and a strong emission around 600 nm. When the dye hinds to DNA by an intercalative mechanism, its emission is greatly enhanced and slightly shifted in wavelength. In the simplest case with ethidium bromide saturating intercalating sites,... 

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