Deoxy thymidine

Deoxy thymidine 2, 3 -dideoxythymidine, I-[(2r)-5c-hydroxy methyl tetrahydro(2r)-... 

Huang P, Farquhar D, Plunkett W. Selective action of 3 -azido-3 -deoxy-thymidine 5 -triphosphate on viral reverse transcriptases and human DNA polymerases. J Biol Chem 1990 265 11914-11918. 

An interesting idea was to use a monolith column to perform dual functions of online SPE and chromatographic separation. Because of the porous structure of a monolith column and its very low backpressure, plasma or diluted plasma can be directly injected. Plumb et al. (2001) used this approach to quantitate an isoquinoline drug and 3 -azido-3 -deoxy thymidine (AZT). Diluted plasma samples (plasma water 1 1) were injected directly into a Chromolith Speed ROD RP-18e column... 

List of Abbreviations PCR, polymerase chain reaction RT-PCR, reverse transcription polymerase chain reaction DNA, deoxyribonucleic acid RNA, ribonucleic acid RNase, ribonuclease mRNA, messenger RNA GABAa, y-aminobutyric acid type A cRNA, copy RNA dNTPs, deoxy nucleoside triphosphates MMLV, Mouse Moloney murine leukemia vims RT, reverse transcriptase bp, base pair Tm, melting temperature DEPC, diethylpyrocarbonate OD, optical density mL, milliliter SA-PMPs, streptavidin paramagnetic particles dT, deoxy thymidine DTT, dithiothreitol DNase, deoxyribonuclease RNasin, ribonuclease inhibitor UV, ultraviolet TBE, Tris-borate, 1 mM EDTA EDTA, ethylenediaminetetraacetic acid Buffer RET, guanidium thiocyanate lysis buffer PBS, phosphate buffered saline NT2, Ntera 2 neural progenitor cells... 

Zervosen A, Elling L, Kula MR (1994) Continuous enzymatic synthesis of 2 -deoxy-thymidine-5 -a-(D-glucopyranosyl) diphosphate. Angew Chem Int Ed Engl 33 571-572... 

The Step 3 product (0.02 mmol) was dissolved in 2 ml of DMF and treated with 3 -azido-3 -deoxy-thymidine (0.04 mmol), 1-hydroxybenzotriazole (0.04 mmol), 4-dimethyla-minopyridine (0.042 mmol), and dicyclohexylcarbodiimide (0.046 mmol) and stirred overnight at ambient temperature. The mixture was filtered, concentrated, precipitated in 2-propanol/diethyl ether, 1 1, and 0.17 g product was isolated. 

The S-pivaloyl-2-thioethyl 5-fluorophosphate derivative of 3 -azido-3 -deoxy-thymidine (24) was synthesised by Perigaud and evaluated for anti-HIV activity in an attempt to improve the biological activity of the mononucleoside 5 -fluorophosphate parent. The fluorophosphotriester was obtained by treating the H-phosphonate diester in pyridine with iodine and triethylamine trihydrofluor-ide. ... 

The synthesis of the water-soluble irreversible inhibitor deoxy-thymidine bromoacetyl-5-p-aminophenylphosphate (III) from the... 

Purines, pyrimidines and their nucleosides and nucleoside triphosphates are synthesized in the cytoplasm. At this stage the antifolate drugs (sulphonamides and dihydrofolate reductase inhibitors) act by interfering with the synthesis and recycling of the co-factor dihydrofolic acid (DHF). Thymidylic acid (2-deoxy-thymidine monophosphate, dTMP) is an essential nucleotide precursor of DNA synthesis. It is produced by the enzyme thymidylate synthetase by transfer of a methyl group from tetrahydrofolic acid (THF) to the uracil base on uridylic acid (2-deoxyuridine monophosphate, dUMP) (Fig. 12.5). THF is converted to DHF in this process and must be reverted to THF by the enzyme dihydrofolate reductase (DHFR) before... 

A new series of 5-carboranyl-substituted-2 -deoxyuridine (25a) and deoxy-thymidine (25b) derivatives containing a range of alkyl spacers has been prepared to access a more effective use of boron neutron capture therapy. Evaluation of these derivatives as substrates for the human thymidine kinases TKl and TK2 showed that a decrease in the length of the spacer (from 8 methylene units to 4) between the carborane moiety and the pyrimidine base resulted in better substrate characteristics. 

TBDMS-0-protected 2 -deoxy-thymidine methanephosphonothioic acid with /7-nitrophenylsulfenyl chloride yielded the mixed disulfide (50). (50) was then treated with triphenylphosphine to yield the symmetric pyrophospho-nothionate (51) and the 3 -0-(S-aryl methanephosphonothionate) nucleoside (52) when an excess of / -nitrophenylsulfenyl chloride was present. ... 

Terasaki T, Pardridge WM. 1988. Restricted transport of 3 -azido-3 -deoxy-thymidine and dideoxynucleosides through the blood-brain barrier. J. Infect. Dis. 158 630-32... 

Lin, T. S. Synthesis and in vitro antiviral activity of 3 -0-acyl derivatives of 5 -amino-2 -deoxy thymidine potential prodrugs for topical application. J. Pharm. Sci. 1984, 73, 1568-1571. 

Thymidine kinase (TK) is an essential enzyme for phosphorylation of deoxy-thymidine and DNA synthesis. In addition, it is the enzyme responsible for activation and-or metabolism of a variety of nucleoside analog drugs (for example DNA chain terminators such as AZT). This enzyme has received significant interest for treatment of herpes simplex virus infections (cf. acyclovir) or mycobacterium infections. In both cases, therapies have been developed that seek to exploit the differences between viral or bacterial TK and human TK. Two forms of thymidine kinase are found in human cells TK1 (cytosolic, active in replicating cells) and TK2 (mitochondrial, constitutively active). Some antiviral-anticancer drugs are metabolized by either one of the isozymes. In some cases, this may be associated with either lack of efficacy or... 

Corresponding to the bases above, common ribonucleosides are named adenosine, guanosine, cytidine, and uridine, respectively. Common deoxyribonucleosides are named deoxyadenosine, deoxyguanosine, deoxycytidine, deoxyuridine, and (deoxy)thymidine, respectively. 

Thymidine kinase is an enzyme that catalyzes the reaction that follows (Figure 22.17) (Deoxy)thymidine + ATP <=> dTMP + ADP... 

When the product obtained from this oxidation of (41) is subsequently hydrolysed by snake venom phosphodiesterase in P OJHaO, a process in which the configuration at phosphorus is retained, and the chirality of the resulting 2 -deoxy-thymidine 5 -[ 0, 0, 0]phosphate analysed by cyclization to the 3, 5 -mono-phosphate, methylation and examination by P n.m.r., it is seen that the replacement of sulphur in (41) by proceeds with inversion at phosphorus, giving (43). Similarly, oxidation of (42) affords (44). Methylation of the potassium 18-crown-6 salt of (43) with methyl iodide gives the (i p)(45) and (5 p)(46) diastereoisomers of the methyl phosphotriester, and (45) gives a signal at higher field in the P n.m.r. spectrum than (46). The results show that little, if any,... 

Cells that are synthesizing DNA mnst also be able to synthesize deoxy thymidine triphosphate (dTTP). The key step in the synthesis is the conversion of dUMP to dTMP via thymidylate synthetase. The reaction reqnires a sonrce of N, -methylene tetrahydrofolate to provide the methyl gronp. In this reaction the tetrahydrofolate is oxidized to dihydrofolate. Dihydrofolate is rednced to tetrahydrofolate via dihydrofolate reductase so more methylene If, A °-tetrahydrofolate is made from serine in a reaction that is catalyzed by serine hydroxymethyltransferase. These three reactions, which are essential for the formation of dTMP, are shown in Fig. 14-20. 

A range of 3 -0-acyl derivatives of 5 -amino-5 -deoxy thymidine have... 

These hydrogen phosphohpids present prodrugs of nucleosides such as 2, 3 -didehydros -deoxy thymidine (d4T) and 2, 3 -dideoxyinosine (ddl), RT inhibitors approved for clinical use to treat human immunodeficiency virus infection. 

The de novo pathway to 2 -deoxythymidine monophosphate (dTMP) synthesis first requires the use of dUMP (2 -deoxyuridine-5 -monophosphate) from the metabolism of either UDP or CDP (cytidine diphosphate). The hydrolysis of dUTP (2 -deoxyuridine-5 -triphosphate) to dUMP and subsequent methylation at C-5 by the action of thymidylate synthase, using A, A i°-methylenetetrahydrofolate (THF) as the methyl donor, generate dTMP (Figure 6.54). The latter is subsequently phosphorylated to deoxy-thymidine triphosphate (dTTP) used in DNA synthesis and repair. 

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