2 -deoxyribonucleoside synthesis

The first step, deoxyribonucleoside synthesis, has been demonstrated in vitro with purified preparations of purine ribonucleoside phosphorylase and thymidine phosphorylase (11-13). However, it is uncertain whether a significant incorporation of base occurs in cells by this route, without an extracellular source of deoxyribosyl groups (see below). The possibility that deoxyribose 1-phosphate may be generated endogenously by way of deoxyriboaldolase is discussed in Section IV. 

Das B, Tokunaga E, Tanaka M, Sasaki T, Shibata N (2010) Perfluoroisopropyl zinc phthalocyanines conjugated with deoxyribonucleosides synthesis, photophysical properties and in vitro photodynamic activities. Eur J Org Chem 2010 2878-2884... 

Two-stage aldolase-based technical process for deoxyribonucleoside synthesis. 

The Pd-mediated coupling involving organomercury and alkenes is useful for the synthesis of C-5 substituted 2 -deoxyribonucleosides[376]. The ethylur-idine 415 is prepared by the reaction of the 5-chloromercuriuridine 414 with... 

Conversion of purines, their ribonucleosides, and their deoxyribonucleosides to mononucleotides involves so-called salvage reactions that require far less energy than de novo synthesis. The more important mechanism involves phosphoribosylation by PRPP (structure II, Figure 34-2) of a free purine (Pu) to form a purine 5 -mononucleotide (Pu-RP). 

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

Figure 36-14. The initiation of DNA synthesis upon a primer of RNA and the subsequent attachment of the second deoxyribonucleoside triphosphate.

During the S phase, mammahan cells contain greater quantities of DNA polymerase than during the nonsynthetic phases of the cell cycle. Furthermore, those eiKymes responsible for formation of the substrates for DNA synthesis—ie, deoxyribonucleoside triphosphates—are also increased in activity, and their activity will diminish following the synthetic phase until the reappearance of the signal for renewed DNA... 

DNA polymerase I is a nonessential enzyme, since viable E. coli mutants lack it (pol A). This conclusion is complicated, however, since the enzyme catalyzes three separate chemical reactions. It polymerizes deoxyribonucleoside triphosphates, and it has two exonucleolytic activities, a 3 to 5 activity and a 5 to 3 activity. The pol A - mutants lack only the polymerization activity. Other mutants lacking both the polymerase and the 5 to 3 exonuclease activity are lethal. Thus the exonuclease function is the more important one. This fits with the role of this enzyme in removing damaged DNA segments (DNA repair) and in removing covalently attached RNA from DNA chains. We will later see that small RNAs serve as primers of DNA synthesis. 

If a deoxyribonucleoside 5 -monophosphate is first esterified with a bulky apolar group, and then used as the 5 -terminus for synthesis of an oligodeoxyribonucleotide, reaction products may conveniently be isolated by solvent-extraction techniques, up to about the tetranucleotide stage. 2-(4-Tritylphenyl)thioethanol (69) and 2-(4-tritylphenyl)sulphonylethanol (70) have been used for this purpose.119 For deblocking, (69) is first oxidized to (70) with iV-chlorosuccinimide and then removed with alkali. 

Using guanosine or 2 -deoxyguanosine as starting material for the synthesis of ribonucleosides or deoxyribonucleosides respectively, the reaction can be driven towards completion by precipitation of the highly insoluble guanine co-product. This approach has... 

Example 6 efficient synthesis of deoxyribonucleoside phosphoroamidite eliminating the use of additional activator has been described by Ravikumar and his associates [27]. 

This synthetic procedure steps a-d can be performed as a one-flask process. The simplicity of this method and its high yield observed makes this approach competitive with the most widely used method based on sulfuriza-tion of phosphite intermediate prepared on phosphoroamidite route. An analogous dithiaphospholane approach was applied earlier for the synthesis of phosphorodithioates derived from deoxyribonucleosides [105]. The oxathiophospholane strategy which allows stereoselective synthesis of P-chi-ral thioanalogues of oligonucleotides was most recently described by Guga, Okruszek and Stec [105]. 

The difficulty in the chemical synthesis of 2 -deoxyribonucleoside lies in the generation of 2-deoxyribosyl groups. The chemical syntheses of 2-deoxyribosyl groups and further to 2 -deoxyribonucleosides involve complex protection and deprotection steps [8-11]. It is likely that the introduction of biochemical reactions with... 

Biochemical Retrosynthesis of 2 -Deoxyribonucleosides from Glucose Acetaldehyde and a Nucleobase Three-Step Multi-Enzyme-Catalyzed Synthesis... 

One-Pot Multi-Step Enzymatic Synthesis of 2 -Deoxyribonucleoside from Glucose, Acetaldehyde and a Nucleobase... 

Purine nucleoside phosphorylase (PNP, E.C. 2.4.2.1) catalyzes the reversible phosphorylysis of ribonucleosides and 2 -deoxyribonucleosides of guanine, hypoxanthine, and related nucleoside analogs [1]. It normally acts in the phosphorolytic direction in intact cells, although the isolated enzyme catalyzes the nucleoside synthesis under equilibrium conditions. Figure 1 shows the chemical reaction. 

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