Nucleosides acid-based hydrolysis

For the removal of this protecting group, tetrabutylammonium fluoride in oxolane is the most frequently used [388, 389, 409-411]. A much simpler reagent to prepare, potassium fluoride — crown ether, has been introduced for the same purpose [427]. Silyl group at 0-2 of nucleosides is cleaved more rapidly [411] than at 0-5. Acyl migrations occurred under the tetrabutylammonium fluoride-catalyzed desilyla-tion [432, 434, 443], Differencies between the primary and secondary position were also observed for acid- or base-catalyzed solvolysis [391, 409-412], 5 -0-(7ert-butyl-dimethylsilyl)nucleosides are much more labile towards acid than either 2 - or 3 -silyl ethers [391, 410-412], whereas the situation is reversed for base hydrolysis [411], /V-Bromosuccinimide in aqueous DMSO is another alternative for the removal of this type of silyl group [444]. 

Nucleic acids, the carriers of genetic information, are macromolecules that are composed of and can be hydrolyzed to nucleotide units. Hydrolysis of a nucleotide gives one equivalent each of a nucleoside and phosphoric acid. Further hydrolysis of a nucleoside gives one equivalent each of a sugar and a heterocyclic base. 

Sephadex has been used to a lesser extent in the nucleic acid field. - The G-50 type will separate RNA of high molecular weight from nucleosides or bases. However, Sephadex does not separate the complex mixture of mono- to hexanucleotides obtained by enzymic hydrolysis of RNA. Sephadex-25 has been used as the supporting medium for partition chromatography of yeast-soluble RNA. ... 

Despite their absence from the current sequence classification, much is known about the mechanisms of A -glycoside formation, hydrolysis and phos-phorolysis at the anomeric centre of o-ribofuranose. The enzymes physiologically are involved in nucleoside and nucleotide biosynthesis and degradation some work at the nucleic acid polymer level to remove or add modified nucleic acid bases. 

In the case of adenine nucleoside derivatives the rate constant for hydrolysis in 0.1 M HCl of 2, 3 -dideoxy-2, 3 -didehydroadenosine is 212 times higher than that of adenosine [107]. The lability of the glycosidic bond of regular and 2, 3 -unsaturated nucleosides depends on the nature of the nucleic acid base and the range of pH [107], but some 2, 3 -unsaturated nucleosides i.e., 78d are unstable at neutral pH in protic solvent solutions [130]. 

When a nucleotide is hydrolysed under appropriate conditions, the phosphate group is split off, leaving the nucleoside. More drastic hydrolysis (e.g. 12 N perchloric acid at 100°C) separates the nitrogen base from the carbohydrate sugar and thus nucleic acids can ultimately be split into their fundamental components (Figure 11.30). 

Nucleosides are stable in water and in dilute base. In dilute acid, however, the glycosidic bond of a nucleoside undergoes hydrolysis to give a pentose and a heterocyclic aromatic amine base. Propose a mechanism for this acid-catalyzed hydrolysis. 

Purine nucleosides are known to be susceptible to acid, giving nucleic acid and D-ribose. This property is based on the hydrolysis of the g ycosidic bond. Treatment with cation-exchange resin in H-form is useful for the industrial isolation or purification of purine nucleosides. The rates of hydrolysis of gluconsine, hypoxanthine, and adenosine with cation exchange resins were compared with the hydrolysis rate with hydrochloric acid. The hydrolysis of adenosine with a cation-exchange resin was slower that that of guanosine, while the reverse was true for hydrolysis with hydrochloric acid this was attributed to the difference in the position of protonation of the two substances. 

Nucleosides are much more water-soluble than the free bases because of the hydrophilicity of the sugar moiety. Like glycosides (see Chapter 7), nucleosides are relatively stable in alkali. Pyrimidine nucleosides are also resistant to acid hydrolysis, but purine nucleosides are easily hydrolyzed in acid to yield the free base and pentose. 

The nucleic acids DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) are biological polymers that act as chemical carriers of an organism s genetic information. Enzyme-catalyzed hydrolysis of nucleic acids yields nucleotides, the monomer units from which RNA and DNA are constructed. Further enzyme-catalyzed hydrolysis of the nucleotides yields nucleosides plus phosphate. Nucleosides, in turn, consist of a purine or pyrimidine base linked to Cl of an aldopentose sugar—ribose in RNA and 2-deoxyribose in DNA. The nucleotides are joined by phosphate links between the 5 phosphate of one nucleotide and the 3 hydroxyl on the sugar of another nucleotide. 

A specific approach for the measurement of base damage to DNA involves the hydrolysis of DNA into monomeric units. Acidic hydrolysis leads to the release of bases while enzymatic treatment yields nucleosides. The resulting mixture of lesions together with the overwhelming presence of normal bases or nucleosides is resolved by chromatography. The targeted damage is then quantified by use of specific detection systems. 

In view of the difficulty of hydrolyzing the pyrimidine nucleosidic linkages, ribonucleic acids have been hydrolyzed to a mixture of purine bases and pyrimidine nucleotides which is then separated by paper chromatography.132, 163 164 This method has been employed extensively for the analysis of ribonucleic acids, and gives reproducible results,166 but it has not been used to any great extent for deoxyribonucleic acids, probably because, under these conditions of hydrolysis, they yield some pyrimidine deoxy-ribonucleoside diphosphates.166... 

Base radical cations are also more acidic than their uncharged forms and the N-1 pAa of G + is 3.9 at the nucleoside level (compared to an N-1 pA a of 9.25 for dG ). Thus, neutral pH deprotonation of G + generates the neutral radical G(—H) that can react with O2 to eventually yield 2,5-diamino-imidazolone (Iz) and its hydrolysis oxazolone derivative In a competitive process, 8-oxoG can also be generated from G( H). ... 

NUCLEOSIDE. A compound of importance in physiological and medical research, obtained during partial decomposition (hydrolysis) of nucleic acids and containing a purine, oi pyrimidine base linked to either tf-ribose, forming ribosides, or rf-deoxyribose, forming deoxynbosides. They are nucleotides minus the phosphorus group. See also Adenosine and Nucleic Acids... 

The first detailed proposal for the mechanism of action of ribonuclease was put forward by Mathias and Rabin and their colleagues (514) An original diagram from their paper is shown in Fig. 28 BIB, 516). It bears a remarkable similarity to the geometry of the active site as defined by the X-ray studies and shown in Fig. 23. For Step 1 the mechanism proposes (1) removal of the proton on the 2 -OH by an imidazole residue in the base form, (2) protonation of the 5 0 of the leaving nucleoside by the other imidazole in the acid form, and (3) attack by the 2 alkoxide on the phosphorus atom to yield the cyclic phosphate. Hydrolysis or alcoholysis of the cyclic phosphate requires the reverse of each of these steps. At the start of step 1, one histidine is in the acidic form and one in the basic form. At the start of step 2 the roles of the two histidine residues are reversed. 

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