Nucleosides examination

Nucleosides examined include 1-allylisoguanosine, 1-allylxanthosine <92MI 711-01), and 3-methyl-adenosine /i-toluene sulfonate <89CPB1208>. 

A number of papers have examined the interaction between platinum complexes and nucleosides. Mono-nucleoside complexes K[Pt(nucleoside)Cl3] (nucleoside = guanosine, inosine, or xanthosine), which are 1 1 electrolytes, have been characterized by chemical analyses and n.m.r. spectroscopy. K2[(PtCl3)2(adenosine)] was also prepared. Various halogenoplatinum nucleoside complexes have been obtained from acidic, neutral, and basic solutions, and the bonding modes of the nucleoside examined using n.m.r. and i.r. spectroscopy.In neutral or weakly acid media adenosine and... 

From the 4 -subsdtuted nucleosides examined thus far, it can be concluded that anti-HTV activity extends over a sizable range of modification if certain positions are left intact. Figure 1 summarizes where changes are tolerated. It appears that in order to retain good activity the 4 -substituted nucleoside must be a 2 -deo y-fi-D-erythro derivative. However, it is remarkable that once these criteria were satisfied, none of the changes of the heterocyclic base resulted in a dramatic loss of activity. Furthermore, as mentioned before, the 4 -substituent could be of different types, although azido and cyano were the most effective. 

For nonvolatile or thermally labile samples, a solution of the substance to be examined is applied to the emitter electrode by means of a microsyringe outside the ion source. After evaporation of the solvent, the emitter is put into the ion source and the ionizing voltage is applied. By this means, thermally labile substances, such as peptides, sugars, nucleosides, and so on, can be examined easily and provide excellent molecular mass information. Although still FI, this last ionization is referred to specifically as field desorption (FD). A comparison of FI and FD spectra of D-glucose is shown in Figure 5.6. 

Both FI and FD provide good molecular mass information, but few if any fragment ions, and allow thermally labile substances such as peptides, nucleosides, and glycerides to be examined, as well as inorganic salts. 

This section examines the synthesis of nucleosides that contain seven-membered sugar analogues in place of the deoxyribose component. Nucleosides from the last group have been further incorporated into ONs via solid-phase DNA synthesis. A physical and biochemical investigation of the oligomers thus prepared continues in the next section. The study under review culminated in the assessment of the ability of the oligomers to complex with single-stranded RNA and for the heteroduplexes so formed to serve as substrates of RNAseH. 

Many of these complexities have come to light during the course of the detailed examination of the photolysis of individual substances they are still too difficult to reduce to generalizations, and will be found discussed here under the headings of the particular pyrimidine and its derivatives. However, the existing information about photoproduct formation in bases, nucleosides, and nucleotides has been summarized in Table I. 

The first, in vivo study on the antitumor activity of ketonucleosides appeared14 in 1977. The action of l-(6-deoxy-2,3-0-isopropylidene-a-L-h/xo-hexopyranosyl-4-ulose)thymine (45) and of 7-(3-0-acetyl-4,6-dideoxy-/ -L-gfi/cero-hex-3-enopyranosyl-2-ulose)theophylline (61a) against LI 210 leukemia in mice was examined comparatively. From the results obtained, it was clear that the unsaturated ketohexosylpurine 61a was much more active than the ketohexosylpyrimidine 45, whereas the parent nucleosides (44 and 34a, respectively) were inactive under the same experimental conditions. 

A thorough study15 of the structure-activity relationship of the four unsaturated ketonucleosides 61a, 68b, 68c, and 72b showed that all of the compounds examined exhibited significant activity against LI 210 leukemia, and the presence of a methyl group on C-5 of the hexose did not appear to be a necessary prerequisite for significant activity. In the meanwhile, nucleosides 68b and 72b proved to be less toxic, and repeated administration of a dose appeared to decrease the toxic effects without affecting the antitumor activity of the compounds. 

In 1964, Tsuda and Strauss discovered a DNase activity in crude extracts of Micrococcus lysodeikticus (later renamed Micrococcus luteus) which required a nucleoside di- or triphosphate for activity (48). This enzyme has recently been purified extensively (2400-fold) and examined in detail by Takagi and his colleagues (49). It has an alkaline pH... 

The enzyme has been partially purified (70-fold) from 38,000 X 9 supernatant fluid from sheep brain homogenates by Ipata (55-58). Thq enzyme (MW 140,000) is reported to be specific for 5 -AMP and 5 -IMP although the substrate specificity does not appear to have been examined closely. 2 - and 3 -AMP are not hydrolyzed (56). Unlike the enzyme from many sources the brain enzyme does not require divalent cations and indeed Co2+, which stimulates several other 5 -nucleotidases, was inhibitory at 5 mM. The enzyme is strongly inhibited by very low concentrations of ATP, UTP, and CTP (50% inhibition by 0.3 pM ATP) but not by GTP. 2 -AMP, 3 -AMP, and a variety of other nucleoside monophosphates, nucleosides, and sugar phosphates do not inhibit. A kinetic examination of ATP, UTP, and CTP inhibition (56-58) revealed that inhibition curves were sigmoidal, indicating cooperativity between inhibitor molecules and an allosteric type of interaction between inhibitor and protein. The metabolic significance of ATP inhibition is... 

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