T1 - Synthesis of a technetium-99m-labeled thymidine analog

The biosynthesis of thymidine triphosphate is obviously more complex than that of any other dNTP given that thymine nucleotides are derived from uracil nucleotides and a methyl group must be created. In most cells, the dUDP produced by rNDP reductase action on UDP is phosphorylated to dUTP by nucleoside diphosphate kinase. dUTP is cleaved by an active pyrophosphatase, deoxyuridine triphosphatase, or dUTPase. This enzyme plays a dual role: (1) Because dUTP is a good substrate for DNA polymerase, dUTPase minimizes the steady-state pool size of dUTP and, hence, helps to exclude dUMP from DNA. (2) The dUTPase reaction is a significant biosynthetic route to dUMP, the substrate for thymidylate synthase.

T1 - Utilization of labeled thymidine in DNA synthesis

Synthesis and Evaluation of α-Thymidine Analogues as …

Synthesis and release of thymidine by macrophages.

However, incorporation of bromodeoxyuridine into DNA is a lethal event. Thus, thymidine kinase deficiency leads to a BrdUrd-resistant phenotype. Because most large DNA viruses encode a thymidine kinase, this is a useful system for manipulating viral genes, for example, the use of vaccinia virus as a vector in the generation of multivalent vaccines (7).

US4914233A - Synthesis of beta-thymidine - Google …

On the other hand, one can select for the presence of active salvage enzymes. The best example is the use of "HAT medium" in somatic cell genetic analysis and in preparing monoclonal antibodies. These techniques involve fusing cells of different origins and culturing in HAT medium to select for those cells that have undergone fusion. HAT is an acronym for the medium’s constituents,— hypoxanthine, aminopterin, and thymidine. Aminopterin inhibits dihydrofolate reductase, blocking the synthesis of tetrahydrofolate needed for de novo synthesis of purine nucleotides and thymidine nucleotides. Thus, cells can grow in HAT medium only if they express active thymidine kinase and HGPRT, for salvage synthesis of thymidine and purine nucleotides, respectively. In monoclonal antibody production, one of the cell lines to be fused lacks thymidine kinase, and the other lacks HGPRT. Thus, only cells resulting from a fusion event have functional copies of both enzymes and can grow.

A comparable selectable marker is the gene encoding thymidine kinase. 5-Bromodeoxyuridine is anabolized similarly to thymidine;

DNA synthesis (Thymine --> Thymidine ..

“Synthesis and Evaluation of Thymidine-5 ’-O-monophosphate Analogues as Inhibitors of Mycobacterium Tuberculosis Thymidylate Kinase.” 12 (19): 2695–2698.

Pyrimidine salvage is catalysed by thymidine kinase.

It is useful to begin our survey of deoxyribonucleotide biosynthesis by considering the processes through which the chemical differences between DNA nucleotides and RNA nucleotides arise. The methyl group of thymine, which distinguishes it from uracil, arises through the transfer of a single-carbon functional group to a uracil nucleotide, catalyzed by thymidylate synthase. The presence of 2-deoxyribose as the sugar in DNA nucleotides rather than the ribose found in RNA comes about through reduction of the ribose sugar on a ribonucleotide substrate (see Ribonucleotide Reductases). Some aerobic bacteria and all anaerobic microorganisms studied carry out this reduction at the ribonucleoside triphosphate (rNTP) level. In all other organisms studied, however, the substrates for ribonucleotide reductase are the ribonucleoside 5′ -diphosphates (rNDPs). Whether a particular reductase acts on rNDPs or rNTPs, a single enzyme reduces all four ribonucleotide substrates. Accordingly, the enzyme interacts with allosteric modifiers to ensure that the four DNA precursors are produced at rates commensurate with the base composition of the organism’s genome. In this article, we will describe the predominant pathways to dNTPs that begin with reduction of rNDPs to deoxyribonucleoside diphosphates (dNDPs). These pathways are summarized in Figure 1.

Thymidine is significant because of its involvement in the biosynthesis of DNA and in the preservation and transfer of genetic information.

DTTP; Deoxy-TTP; Thymidine 5'-triphosphate; ..

The synthesis of vaccinia virus-induced thymidine kinase is normally arrested several hours after infection. In thymidine kinase-deficient LM cells infected with IHD strain of vaccinia virus, arrest occurs whether or not viral DNA synthesis is inhibited. With virus inactivated by UV irradiation, enzyme synthesis takes place, but arrest is abolished. It is suggested that an early viral genetic function is responsible for the cessation of thymidine kinase synthesis.

Aug 26, 2016 · Glutaminase 1 inhibition reduces thymidine ..

Thymidine kinase, DNA synthesis and cancer | …

. Now the deoxyribose-1-phosphate can react with another base in anucleoside phosphorylase-catalyzed reaction proceeding in the reverse direction, eg,Thymidine can then become a nucleotide via the thymidine kinase reaction leading to dTMP. Although this process can significantly change relative dNTP pool sizes, it does not involve net deoxyribonucleotide synthesis; rather, it involves redistribution of the deoxyribosyl units linked to purine and pyrimidine bases.

Thymidine monophosphate - Revolvy

Thymidine Analogues for Tracking DNA Synthesis - MDPI

T1 - Synthesis, anti-HIV activity, and resistance profile of thymidine phosphonomethoxy nucleosides and their bis-isopropyloxymethylcarbonyl (bisPOC) prodrugs