Polynucleotides. XXIV. Synthesis and properties of a dinucleoside monophosphate derived from 8,2'-O-cycloadenosine.
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Although magnesium fulfills several essential biochemical roles, direct studies on this ion are complicated by its unfavorable spectroscopic characteristics. This contribution explores the possibility of monitoring magnesium-nucleic acid binding via a combination of [Co(NH3)6]3+ as surrogate for [Mg(H2O)6]2+, and of high-resolution solid-state 59Co NMR as a spectroscopic probe. Such strategy quenches fast cationic exchanges between bound and free states, while exploiting the superior NMR properties of the 59Co spin. Experiments on relatively small amounts of tRNA can then discern resonances corresponding to different metal binding environments. These characterizations were assisted by studies on model compounds and by multinuclear 31P-59Co recoupling experiments.
Preliminary studies are reported on the synthesis and testing of substituted vinyl polymers that are designed to have sequence specific affinity for polyribonucleic acids. Copolymers of 1-vinyluracil with acrylic acid, 2-methylacrylic acid, or 1-vinyl-2-pyrrolidone were prepared by gamma-irradiation to give the respective polymers 1,3, and 4. Similarly, 9-vinyladenine yielded copolymeric products 5 and 6 with acrylic acid or 2-methylacrylic acid. Radical initiated polymerization of 9-vinyladenine with acrylamide yielded copolymer 7. The products were characterized by elemental analysis and ultraviolet, infrared, and nuclear magnetic resonance spectroscopy. No hypochromicity could be detected on mixing polymers 1-4 with poly(adenylic acid). The acrylic acid copolymer 2 containing a high ratio of vinyluracil was a potent inhibitor of poly(adenylic acid) coded polylysine synthesis in an in vitro system. Polymers 6 and 7, containing a high proportion of vinyladenine, inhibited poly(uridylic acid) coded poly(phenylalanine) synthesis.
A recently developed methodology [Jankowiak, R., Lu, P., Small, G. J., and Geacintov, N. E. (1990) Chem. Res. Toxicol. 3, 39-46], which combines fluorescence line narrowing spectroscopy at 4.2 K with non-line-narrowed (S2----S0 laser excitation) fluorescence spectroscopy at 77 K and fluorescence quenching, is used to characterize adducts formed from (+)-anti-BPDE and the alternating copolymers poly(dG-dC).poly(dG-dC) and poly(dA-dT).poly(dA-dT), the nonalternating poly (dG).poly(dC), single-strand poly(dG), and the oligonucleotide d(ATATGTATA). Detailed comparisons of the fluorescence spectra and quenching (with acrylamide) of the properties of the adducts with those of (+)-anti-BPDE-DNA adducts are made. Fluorescence spectra of the trans and cis isomers of the adduct formed from guanosine monophosphate and the adducts of d(ATATGTATA) are used to assign the stereochemistry of the two major DNA adducts as trans-N2-dG moieties which occupy two different DNA sites. Evidence for the existence of minor cis-type guanine adducts is provided. Finally, a fourth type of DNA adduct (minor) is identified and assigned as trans-N6-dA.
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Pentafluoropyridine reacts with thymidine, adenosine, and uridine hydroxy groups to give quantitative yields of the corresponding nucleoside di- and triaryl ethers. The nucleophilic substitution reactions proceed successively and in parallel, with the slowest step being the nucleophilic substitution of the nucleoside secondary hydroxyls. The resulting ethers contain tetrafluoropyridyl moieties, which could be smoothly modified by nucleophilic substitution of fluorine atoms. The ethers are useful intermediate synthons (both isolated and in situ) for molecular design of oligonucleotide analogues. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.
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