Photochemistry of nucleic acids, nucleic acid derivatives and related compounds.
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In order to investigate the effect of the Pt(II) ion on the stacking interaction between tryptophan and a guanine base, the quenching of Trp fluorescence was monitored for some systems in the absence and presence of the metal ion, and the association constants were obtained by the analysis of Eadie-Hofstee plots. All spectral data suggested that the stacking interaction is enhanced by the Pt(II) coordination to the guanine N7 atom. The result indicates the importance of the metal ion as a bookmark in the specific recognition of a nucleic acid base by an aromatic amino acid residue.
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Nucleic acid gels can be formed as a result of the cross-linking action of ultraviolet light or of nitrous acid. Such gels form duplex combinations with complementary nucleic acid strands.
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Raman spectra of fibers of DNA that have been prepared in the A, B, and C forms are presented and compared with Raman spectra of DNA and RNA in dilute solution. It is shown that the phosphate vibrations in the region 750-850 cm(-1) are very sensitive to the specific conformation of the phosphate group in the backbone chain and are virtually independent of all ohter factors. Thus, a very simple method for the determination of the specific conformation of the backbone chain of nucleic acids, at least so far as the sugar-phosphate chain is concerned, appears available. The method is applied to short oligomers and dimers of ribonucleosides. It is found that at low temperatures, at pH 7, the phosphate group goes into the geometry of the A conformation when the stacking forces between the bases are sufficiently strong.
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Nucleic acids (DNA and RNA) have been discovered in the kinetoplast of free-living Bodonina: Bodo caudatus, Pleuromonas jaculans, Rhynchomonas nasuta--by means of cytochemical methods. The kinetoplast has variable contents of nucleic acids whose chemoarchitectonics is due to their non-homogeneous distribution within the kinetoplast. The Feulgen reaction in the kinetoplast is more intensive than in the nucleus. Kinetoplast is closely connected with the cytoplasmic RNA metabolism. Many individuals of R. nasuta were found to have two kinetoplasts, no other signs of cell division being observed. P. jaculans has up to 45% of dyskinetoplastic forms.
Space-filling molecular models have been used to examine structural analogies between amino acids and nucleic acids. The three-dimensional structures of amino acid R groups appear to be stereochemically related to cavities formed by removal of single bases in double helical nucleic acids. The common L amino acids may thus be complementary to their codons.
Nucleic acids are elucidated in configuration space. An algorithm relating sequence to stability in A and B helical secondary structures, is stated to incorporate NMR conformational and optical melting data. This made possible a classification of elementary sequences in terms of configuration forces driving between A and B states, a finding useful in prediction of structural behavior of different sequences of DNA, RNA and their hybrids.
The action of two types of ascorbate-related reductones on nucleic acids was investigated by comparison with that of ascorbic acid (AsA). Amino reductone (ScA) and thiol reductone (MHC) caused strandscissions in nucleic acids. This was confirmed by the fact that reductones lowered the viscosity of DNA solution and shifted the peaks of DNA and RNA to the low molecular side in centrifugal profile. Cu2+ strengthened their action as in the case of enediol reductones. The braking activity of thiol reductone is relatively wesk compared with those of amino and enediol reductones. The preferential degradation of spurinic acid was caused with amino and thiol reductones, suggesting that pyrimidine clusters in nucleic acids were susceptible to breakage.
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From submerged cultures of Lachnella villosa, Lachnella sp. 541, and Peniophora laeta we isolated marasmic acid (1), a metabolite first described from surface cultures of Marasmius conigenus. The sesquiterpenoid exhibits potent antimicrobial and cytotoxic properties. In cells of the ascitic form of Ehrlich carcinoma RNA and DNA syntheses are preferentially inhibited. Marasmic acid inhibits RNA synthesis in isolated nuclei, but does not interfere with the transport of nucleoside precursors into the cells. RNA polymerase II and capping enzyme (mRNA guanylyltransferase), two enzymes of nucleic acid metabolism, are markedly affected after preincubation with marasmic acid. We assume that marasmic acid acts on nucleic acid syntheses by direct inhibition of some of the enzymes involved. This mode of action would also explain its mutagenic properties. The preparation and testing of two derivatives, 2 and 3, revealed that the alpha,beta-unsaturated aldehyde is essential for the antimicrobial and cytotoxic activity of marasmic acid.
DNA synthesis in Epstein-Barr virus (EBV)-infected lymphocytes was inhibited by phosphonoacetic acid (PAA) as measured by [3H]thymidine incorporation. PAA, at a concentration of 200 microgram/ml, inhibited [3H]thymidine incorporation by human umbilical cord lymphocytes infected with EBV strain P94 but had little effect on DNA synthesis in mitogen-stimulated cells. Transformed cell lines did not develop from infected cord cell cultures treated with 100 microgram of PAA per ml. Cytofluorometric analysis showed marked increases in cellular nucleic acid content (RNA plus DNA) as early as 9 days after infection of cord cells in the absence of PAA and before significant enhancement of [3H]thymidine incorporation became apparent. Moreover, EBV led to increases in cellular nucleic acid even when 200 microgram of PAA per ml was added to cell cultures before infection. The apparent discrepancy between results obtained by [3H]thymidine incorporation and cytofluorometry is explained either by significant inhibition of cellular DNA polymerases by PAA or by a block at the G2 + M phase of the cell cycle. The data suggest that EBV initiates alterations in cellular nucleic acid synthesis or cell division without prior replication of viral DNA by virus-induced DNA polymerases.
Water soluble polyethyleneimine derivatives containing nucleic acid bases were found to interact with polynucleotides, DNA, RNA. The conformational change by formation of complex was observed by CD spectra and was discussed with the hypochromicity in UV spectra. The rates of interactions between nucleic acid bases in polymers were slow as shown by UV spectra, but the conformational changes of the polynucleotides were fast as shown by CD spectra. In the case of the uracil derivative (PEI-Hse-Ura), high value of CD spectra [theta] 2.80 = -8.0 x 10(-4) for the complex with DNA might be caused by psi type conformation of DNA.