Bases, nucleoside

Nucleic acid bases are often analysed in the presence of the corresponding nucleosides since the preferred chromatographic modes are suitable for the simultaneous separation of both classes of compounds. Originally the polar character of the nucleoside bases was exploited using ion-exchange HPLC (Floridi et al., 1977) however, reversed phase techniques are now more commonly employed. 

In two of the most thorough investigations into chromatographic techniques for the separation of nucleoside bases, nucleosides and other UV-absorbing compounds, the retention data for 86 compounds on a reversed phase column has been reported both qualitatively 

6) and ending with 0.05 M phosphate buffer (pH 5.6)-methanol-water (50 25 25). The application of this technique to samples of urine from a Lesch-Nyhan syndrome patient is shown in Fig. 11.1.2. Eluted components were monitored by a UV detector at 254 nm and 280 nm and permits detection of 5-10 pmol of each component. The metabolic fate of radiolabelled precursors can be monitored by using a radioactivity detector (Webster and Whaun, 1981). 

A similar example in which 5-fluorouracil has been included demonstrates the wide appUcability of reversed phase systems coupled with aqueous phosphate buffers for the separation of nucleoside bases (Miller et al., 1982). This study also includes a useful comparison of nine different analytical reversed phase columns in combination with different isocratic conditions and clearly demonstrates subtle differences between them. The study concluded that the best stationary phase to maximise the resolution of the test compounds was Spheri-sorb ODS-2 in combination with ammonium phosphate (pH 3.5) as eluent buffer (Fig. 11.1.3). 

Methanol or acetonitrile are occasionally used as organic modifiers in the reversed phase separations of nucleoside bases and have the 

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Protective group chemistry for these amines has been separated from the simple amines because chemically they behave quite differently with respect to protective group cleavage. The increased acidity of these aromatic amines makes it easier to cleave the various amide, carbamate, and sulfonamide groups that are used to protect this class. A similar situation arises in the deprotection of nucleoside bases (e.g., the isobutanamide is cleaved with methanolic ammonia ), again, because of the increased acidity of the NH group. 

Schuetz JD, Connelly MC, Sun D, Pai-bir SG, Flynn PM, Srinivas RV et al. MRP4 A previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nature Med 1999 5(9) 1048—1051. 

Table XIX contains stability constants for complexes of Ca2+ and of several other M2+ ions with a selection of phosphonate and nucleotide ligands (681,687-695). There is considerably more published information, especially on ATP (and, to a lesser extent, ADP and AMP) complexes at various pHs, ionic strengths, and temperatures (229,696,697), and on phosphonates (688) and bisphosphonates (688,698). The metal-ion binding properties of cytidine have been considered in detail in relation to stability constant determinations for its Ca2+ complex and complexes of seven other M2+ cations (232), and for ternary M21 -cytidine-amino acid and -oxalate complexes (699). Stability constant data for Ca2+ complexes of the nucleosides cytidine and uridine, the nucleoside bases adenine, cytosine, uracil, and thymine, and the 5 -monophosphates of adenosine, cytidine, thymidine, and uridine, have been listed along with values for analogous complexes of a wide range of other metal ions (700). Unfortunately comparisons are sometimes precluded by significant differences in experimental conditions.

Access to modified nucleosides. Base-modified nucleosides and nucleotides are very important for their biological properties. They can be found as antiviral agents (HBH, VZV, AIDS),93 95 in the study of DNA degradation,96,97 as fluorescent agents and as chemical probes of DNA structure.98 101 The access to nucleosides can be achieved by different methods ... 

Selective functionalization of the 7-hydroxyl group as the monomethoxytrityl (MMT) ether and phosphoramidite formation at 0-5 under standard conditions delivered 234 (58% over two steps). This material could be taken through to the solid-phase ON synthesis. This synthesis utilizing 234 and 235 as starting materials delivered homopolymers, 0T15 and oA15, each of which was 15 nucleoside bases long. 

Fig. 7.1.1 Structure of the naturally occurring purine (deoxy)ribonucleosides and nucleoside bases...

Bacterial contamination of the urine may result in strongly increased levels of uracil due to the bacterial degradation of pseudouridine. Thymine-uraciluria, which is indicative of a dihydropyrimidine dehydrogenase or dihydropyrimidinase deficiency, may also result from increased tissue degradation. However, the latter situation is also characterized by hyper-/l-aminoisobutyric aciduria and hyper-/f-alaninuria [6]. Under alkaline conditions, due to the presence of bacterial contamination, the de-oxynucleosides may be hydrolyzed toward their corresponding nucleoside bases. 

Nucleosides based on [l,2,4]triazolo[l,5-a]pyridine can be prepared by reaction between 3-nitro-2-pyridylhydrazine and the thioformimidate 48 followed by ammonolysis.62,63 A tetrahydrotriazolopyridinium salt (49) results from a reaction between a diazenium salt and an anil.64... 

Viswanadhan, V. N., et al., Assessment of Methods Used for Predicting Lipophilicity Application to Nucleosides and Nucleoside Bases. J. Comput. Chem., 1992 14, 1019— 1026. 

Ma M, Zhao S, Li S, Yang Y, Shi J, Fan X, He L (2007) Bromophenols Coupled with Nucleoside Bases and Brominated Tetrahydroisoquinolines from the Red Alga Rhodomela confervoides. J Nat Prod 70 337... 

Figure 15.3 Nucleotides that have been spin-labeled by postsynthetic modification of the oligomer at either the base (A), the sugar (B), the internal phosphodiester (C), or the terminus (D). B indicates the nucleoside base.

Nucleosides Adding the Nitrogenous Bases When we add a nitrogenous base to the sugar, we get a nucleoside, which is sometimes called a nucleoside base. 

So, there are four DNA nucleoside bases deoxyadenosine, deoxythymidine, deoxycytidine, and deoxyguanosine. Usually, these bases are represented as dA, dT, dC, and dG, respectively. Often times, the little d (which stands for de-oxy) is omitted, and we simply use A, T, C, and G when describing the primary... 

If we attach the nitrogenous bases to a ribose, we have the RNA nucleosides. The four RNA nucleoside bases are adenosine, uridine, cytidine, and guanosine. Usually, these nitrogenous bases are represented as A, U, C, and G, respectively. Figure 12.69 gives the names and structures of these compounds. Addition of a phosphate group to carbon 5 of the ribose sugar affords the RNA nucleotide bases. 

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