Deoxy ribonucleoside diphosphate

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... 

Ribonucleotide reductase ribonucleoside diphosphate reductase) is a multisubunit enzyme (two identical B1 subunits and two identical B2 subunits) that is specific for the reduction of nucleoside diphosphates (ADP, GDP, CDP, and UDP) to their deoxy-forms (dADP, dGDP, dCDP, and dUDP). The immediate donors of the hydrogen atoms needed for the reduction of the 2-hydroxyl group are two sulfhydryl groups on the enzyme itself, which, during the reaction, form a disulfide bond (Figure 22.12). 

Deoxyribonucleotides. A chain involving NADPH, a flavoprotein, thioredoxin, and ribonucleotide reductase converts either the ribonucleoside diphosphates or triphosphates to the corresponding 2-deoxy forms (step j, Fig. 25-14) as indicated in Eq. 25-16. 

The synthesis of DNA is dependent on a ready supply of deoxyribonucleotides. The substrates for these are the ribonucleoside diphosphates ADP, GDP, CDP, and UDP the enzyme responsible for the reduction of these substrates to their corresponding deoxy derivatives is ribonucleotide reductase, which has thioredoxin as a cosubstrate. 

Deoxy-2 -fluoromethylene nucleosides are potential inhibitors of ribonucleoside diphosphate reductase (RDPR), which catalyzes the essential biosynthesis path of deoxyri-bonucleoside in the DNA synthesis system. Initial hydrogen abstraction at the C-3 position by tyrosyl radical has been proposed for the RDPR catalysis system (see from 71 to 73 in... 

When the nitrate ester 277 was treated with BuaSnD and AIBN, the deuteriated alcohol 278 was formed, by 1,5-radical translocation. However, the 2 -chloro-2 -deoxy-system 279 gave the furanone 280 under the same conditions. These results suggest that the inhibition of ribonucleoside diphosphate reductase by 2 -chloro-2 -deoxynucleosides involves loss of Cl from a radical at C-3. Some related studies from the same team, also supporting this conclusion, were mentioned earlier. ... 

Scheme 14.11. A proposal for the use of ribonucleoside diphosphate reductase (ribonucleotide diphosphate reductase, EC 1.17.4.1) to convert adenosine diphosphate (ADP), uridine diphosphate (UDP), and cytidine diphosphate (CDP) into their respective 2 -deoxy analogues deoxyadenosine diphosphate (dADP),deoxyuridine diphosphate (dUDP),and deoxy-cytidine diphosphate (dCDP), or, in general, ribonucleic acids (RNAs) into the corresponding deoxyribonucleic acids (DNAs) (after Stubbe, J. 7. Biol. Chem., 1990,265, 5330).

A new synthesis of 3 -deoxy-3 -nitrothymidine involves displacement of an up -iodo-substituent by nitrite ion in DMSO in the presence of phloroglucinol. The (hydroxylamino)nucleoside 65 has been made by reduction of a C-3 nitrone with NaBHsCN, and related 0-alkylhydroxylamines were also described, prepared by reduction of O-alkyloximes. Similar O-alkyloximes at both C-2 and C-3 of uridine have been prepared as potential inhibitors of ribonucleoside diphosphate reductase. ... 

The purine (Pu or R for short) and pyrimidine (Py or Y for short) bases, are connected by a N-glycosidic linkage to the C-T of the pentose sugar, either a ribose in RNA or a 2 -deoxyribose in DNA. The base-(2 -deoxy)ribose unit is called a nucleoside (ribonucleoside or 2 -deoxyribonucleoside). When a nucleoside is phosphorylated either at the 3 -OH or 5 -OH, it is called 3 -nucleotide (Np) or S -nucleotide (pN), respectively. The number of phosphate groups, for example, at the 5 -OH of adenosine, determines whether the nucleotides are designated as adenosine 5 -wo ophosphate (AMP), adenosine 5 -diphosphate (ADP), and... 

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