Purine bases derivation

Cyclic nucleotides are purinic base derivatives with powerful biological activity. It is widely accepted that cyclic nucleotides mediate many of the intracellular biochemical events triggered by neurotransmitters and hormones (1,2). Therefore, the analysis of these compounds carries special relevance in biological sciences. A wide variety of techniques has been developed for cyclic nucleotide assays including binding to phosphokinase (3,4) or to antibodies (5) activation of enzymes... 

Free purine bases, derived from the turnover of nucleotides or from the diet, can be attached to PRPP to form purine nucleoside monophosphates, in a reaction analogous to the formation of orotidylate. Two salvage enzymes with different specificities recover purine bases. Adenine phosphorihosyltransferase catalyzes the formation of adenylate... 

Purine base derivatives as indicators of damage to DNA 02CL276. 

Turel L, Pecanac M., Golobic A., Alessio E., Serli B., Bergamo A., Sava G., Solution, solid state and biological characterization of ruthenium(lll)-DMSO complexes with purine base derivatives, J. Inorg. Biochem., 98, 393-401, 2004. 

In 2011, Coleman demonstrated that p-sulfonatocalix[4]arene-capped AgNPs interact with nucleobases [112]. The nanoparticles discriminate between pyrimidine and purine-based derivatives. The binding efficiency was ascribed to the self-assembly of the macrocycles on the metal surface in an up-down fashion. Macrocycles with the sulfonate functions that bind the guest alternate with those with the sulfonate moieties attached to the silver nanoparticle G ig. 37.18). 

Section 28 2 Nucleosides are carbohydrate derivatives of pyrimidine and purine bases The most important nucleosides are derived from d ribose and 2 deoxy D ribose... 

Section 28.2 Nucleosides are car bohydrate derivatives of pyrimidine and purine bases. 

As is well-known, nucleic acids consist of a polymeric chain of monotonously reiterating molecules of phosphoric acid and a sugar. In ribonucleic acid, the sugar component is represented by n-ribose, in deoxyribonucleic acid by D-2-deoxyribose. To this chain pyrimidine and purine derivatives are bound at the sugar moieties, these derivatives being conventionally, even if inaccurately, termed as pyrimidine and purine bases. The bases in question are uracil (in ribonucleic acids) or thymine (in deoxyribonucleic acids), cytosine, adenine, guanine, in some cases 5-methylcytosine and 5-hydroxymethylcyto-sine. In addition to these, a number of the so-called odd bases occurring in small amounts in some ribonucleic acid fractions have been isolated. 

The analogs of pyrimidine and purine bases can be derived by purely formal structural modifications or, more rationally, from the results of biochemical investigation. 

An important group of antimetabolites are the aza analogs of pyrimidine and purine bases which are theoretically derived by a replacement of the methine group of a pyrimidine or purine nucleus with a nitrogen atom. This replacement represents a relatively minor alteration of the structure of these substances as it does not change the functional groups, practically preserves the molecular weight, and produces almost isosteric compounds. The replacement of the methine... 

The names of 2-aza analogs are derived by formal substitution of the methine group in the 2-position of the purine skeleton by a nitrogen atom (140). Since this position is substituted in some purine bases, only the aza analogs of adenine or hypoxanthine are amenable to such formal derivation. 

This synthetic procedure was used without any significant changes for the preparation of the greatest number of derivatives of t -tria-zolo [4,5-d] pyrimidine. Roblin et prepared the aza analogs of the principal purine bases 8-azaguanine (151), 8-azaadenine (152), 8-azaxanthine (153), and 8-azahypoxanthine (154). By similar methods,... 

Methotrexate belongs to the class of antimetabolites. As a derivative of folic acid it inhibits the enzyme dihydrofolate reductase resulting in a decreased production of thymidine and purine bases essential for RNA and DNA synthesis. This interruption of the cellular metabolism and mitosis leads to cell death. 

The mono-silylated or free acetamides, which are liberated during silylation with 22 a, can, furthermore, interfere with any subsequent reaction, e.g. with electrophiles. Thus in the one-pot/one-step silylation, Friedel-Crafts catalyzed, nucleoside synthesis starting from protected sugar derivatives and pyrimidine or purine bases, the mono- or bis-silylated amides such as 22 a can compete with less reactive silylated heterocycHc bases for the intermediate electrophilic sugar cation to form protected 1-acetylamino sugars in up to 49% yield [42, 47]. On silylation with trimethylsilylated urea 23 a the Hberated free urea is nearly insoluble in most solvents, for example CH2CI2, and thus rapidly precipitated [43]. 

Treatment of the allylic sulfoxide 1227 a with diisopropylethylamine (DIPEA) or of 1227 b with N-trimethylsilyldiethylamine 146 and TMSOTf 20 leads in ca. 90% yield to the quaternary amino derivatives 1228 and 1229 and HMDSO 7 [36] (Scheme 8.15). Tetramethylene sulfoxide 1230 reacts with silylated thymine 1231 in the presence of three equivalents of TMSOTf 20 to give the 4 -thio-nucleoside analogue 1232 and HMDSO 7 [37]. Other silylated pyrimidine, pyridine, and purine bases react analogously with cyclic sulfoxides to give 4 -thio-nucleoside analogues [37, 37a, 38]. 

Analogous photoadditions have been observed on irradiation of pyrimidine and purine bases in ethers and amines. Irradiation of 1,3-dimethylur-acil (314) in tetrahydrofuran leads to the formation of 5- and 6-(tetrahydro-furan-2-yl)-5,6-dihydrouracils 315 and 316.261 Similarly, solvent adducts arising by way of initial hydrogen abstraction have been obtained on irradiation of pyrazine derivatives in diethyl ether or tetrahydrofuran.262 The... 

One of the most important reactions of purines is the bromination of guanine or adenine at the C-8 position. It is this site that is the most common point of modification for bioconjugate techniques using purine bases (Figure 1.53). Either an aqueous solution of bromine or the compound N-bromosuccinimide can be used for this reaction. The brominated derivatives then can be used to couple amine-containing compounds to the pyrimidine ring structure by nucleophilic substitution (Chapter 27, Section 2.1). 

Of the purine nucleosides, dATP may be derivatized at its N-6 position using a long linker arm terminating in a detectable group without losing the ability to be enzymatically incorporated into DNA probes. By contrast, if modification is done at the C-8 position of purine bases, DNA polymerase cannot by used to add the labeled monomer to an existing strand. C-8 derivatives, however, can be added at the 3 terminal using terminal transferase enzyme. 

Figure 27.1 Three common nucleoside triphosphate derivatives that can be incorporated into oligonucleotides by enzymatic means. The first two are biotin derivatives of pyrimidine and purine bases, respectively, that can be added to an existing DNA strand using either polymerase or terminal transferase enzymes. Modification of DNA with these nucleosides results in a probe detectable with labeled avidin or streptavidin conjugates. The third nucleoside triphosphate derivative contains an amine group that can be added to DNA using terminal transferase. The modified oligonucleotide then can be labeled with amine-reactive bioconjugation reagents to create a detectable probe.

Deoxyribonucleic acids readily undergo hydrolysis whereby purine bases are removed to give a derived polynucleotide originally named thymic acid, but now often called apurinic acid. Hydrolysis may be carried out with dilute mineral acid, but recently apurinic acids have been prepared by fission at room temperature with an acidic, ion-exchange resin.236 Under carefully controlled conditions, removal of the purines can be performed quantitatively without destroying the polynucleotide nature of the material and without altering the inter-pyrimidine ratios of the original material.23 ... 

Sulfoxides have also been used in the synthesis of nucleoside analogs (Scheme 3.2). Chanteloup and Beau reported the synthesis of ribofuranosyl sulfoxide 13 and its use in the glycosylation of a series of silylated pyrimidine and purine bases.7 Although 16 is not an anomeric sulfoxide, its reaction with cytosine derivative 17 is conceptually related.8... 

Comparing electrochemical behavior and biological transformations of purine bases, Japanese chemists (Yao and Musha 1974, Ohya-Nishiguchi et al. 1980) have considered the anion-radicals of purine, its 8-deutero and 6,8-dideutero derivatives. As it turned out, up to 40% of the total spin density is localized in position 6 of the purine anion-radical (see Scheme 3.7). Ohya-Nishiguchi et al. (1980) noted that such a large localized spin density is very rare in a n electron system of the purine s size and should have important application in relation to its chemical reactivity. Protonation should... 

The bases that occur in nucleic acids are aromatic heterocyclic compounds derived from either pyrimidine or purine. Five of these bases are the main components of nucleic acids in all living creatures. The purine bases adenine (abbreviation Ade, not A ) and guanine (Gua) and the pyrimidine base cytosine (Cyt) are present in both RNA and DNA. In contrast, uracil (Ura) is only found in RNA. In DNA, uracil is replaced by thymine (Thy), the 5-methyl derivative of uracil. 5-methylcyto-sine also occurs in small amounts in the DNA of the higher animals. A large number of other modified bases occur in tRNA (see p. 82) and in other types of RNA. 

In the most important degradative pathway for adenosine monophosphate (AMP), it is the nucleotide that deaminated, and inosine monophosphate (IMP) arises. In the same way as in GMP, the purine base hypoxanthine is released from IMP. A single enzyme, xanthine oxidase [3], then both converts hypoxanthine into xanthine and xanthine into uric acid. An 0X0 group is introduced into the substrate in each of these reaction steps. The oxo group is derived from molecular oxygen another reaction product is hydrogen peroxide (H2O2), which is toxic and has to be removed by peroxidases. 

The purine bases either alone or in combination as nucleic acids or their derivatives and components are practically unaffected by biologically effective doses of ultraviolet light. Over 90% of the purine bases can be isolated from DNA exposed to enough light to destroy 80-90% of the pyrimidine components.7... 

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