A-thymidine

More recendy, analogues having peptide-based linkers have been explored. A thymidine glycine copolymer (28) has been synthesized in high yield and forms a stable duplex with its cognate single-stranded partner (46). 

Whereas imidazolides of nucleotides react only in organic solvents with phosphates or pyrophosphates to give the corresponding anhydride derivatives in high yield, ATP can also be formed enzymatically in aqueous solution from AMP-Im with inorganic pyrophosphate in the presence of valyl-f-RNA synthetase.[66] A variant of this method is the one-pot reaction of a nucleoside with phosphoryltristriazole and tributylammonium pyrophosphate. 671 An a-methylphosphonyl-/ ,y-diphosphate of a thymidine derivative has been synthesized in a similar way t681... 

A difluorophosphate can be obtained from a phosphorous diimidazolide as demonstrated by the synthesis of a thymidine 5 -difluorophosphate. The diimidazolide was constructed from 3 -dimethoxytritylthymidine and triimidazolylphosphine.[202],[203]... 

Shoji A, Hasegawa T, Kuwahara M et al (2007) Chemico-enzymatic synthesis of a new fluorescent-labeled DNA by PCR with a thymidine nucleotide analogue bearing an acridone derivative. Bioorg Med Chem Lett 17 776-779... 

In view of bcl-2 s major neuroprotective and neurotrophic roles, a study was undertaken to determine if lithium, administered at therapeutically relevant concentrations, affects neurogenesis in the adult rodent brain. To investigate the effects of chronic lithium on neurogenesis, mice were treated with therapeutic lithium (plasma levels 0.97 0.20 mM), for 4 weeks. After treatment with lithium for 14 days, the mice were administered single doses of BrdU (bromodeoxyuridine, a thymidine analog which is incorporated into the DNA of dividing cells) for 12 consecutive days. Lithium treatment continued throughout the duration of the... 

In a rare example of the use of phenylselenides as radical precursors in the generation of alkene radical cations by the fragmentation approach, Giese and coworkers generated a thymidine C3/,C4/ radical cation by expulsion of diethyl phosphate. Trapping experiments were conducted with methanol and with allyl alcohol (Scheme 16), when nucleophilic attack was followed by radical cyclization [66]. 

Scheme 16 Generation and trapping of a thymidine C3, C4 radical cation...

A second relevant enzyme to 5-FU metabolism is thymidylate synthetase (TYMS). If this enzyme is complexed with 5-FU metabolites along with 5,10-methylene-tetrahydrofolate, it cannot maintain a thymidine-5 -monophosphate pool required for DNA replication and repair. A tandem repeat polymorphism in the 5 -promoter region of the TYMS gene can increase enzyme expression (85,86). Tumors carrying the repeats have higher enzyme expression, resulting in lower response to chemotherapy compared to wild type (87). 

Stavudine (d4T, Zerit) is a thymidine nucleoside analogue that is active against HIV-1 and HIV-2. It is approved for the therapy of HIV infection as part of a multidrug regimen and is also used for postexposure prophylaxis. 

Helene110 says that thymidine fluorescence from aqueous solutions at 77°K of a thymidine-adenosine mixture (as well as the identical fluorescence from rigid solutions of G + T, AcC + T or C + T) is owing to a triplet energy transfer to the thymidine moiety. The order of triplet-state energies among the purines and pyrimidines is given as... 

It is a thymidine analogue. After phosphorylation in body zidovudine triphosphate selectively inhibits viral reverse transcriptase i.e. RNA dependent DNA polymerase. It is effective against retrovirus only. 

Telbivudine is a thymidine nucleoside analog with activity against HBV DNA polymerase. It is phosphorylated by cellular kinases to the active triphosphate form, which has an intracellular half-life of 14 hours. The phosphorylated compound competitively inhibits HBV DNA polymerase, resulting in incorporation into viral DNA and chain termination. It is not active in vitro against HIV-1. 

Fig. 5.2.2 Electropherograms for the same genetic region of a homozygous DNA and heterozygous DNA is shown. The sequence of the gene is read from left to right. Up to nucleotide number 4 the sequences are identical. At position number 4, the homozygous DNA has a cytidine on both chromosomes, while the heterozygous DNA has a cytidine only on one chromosome and a thymidine on the other chromosome...

Acyclovir (ACV) is not a true nucleoside, because the guanine residue is attached to an open-chain structure, but it mimics deoxyribose well enough for the compound to be accepted as a substrate by a thymidine kinase specified by certain herpes-type viruses. The normal thymidine kinase in mammalian cells does not recognize ACV as a substrate, however, so only virus-infected cells convert ACV to its monophosphate. Once the first phosphate has been added, the second phosphate is added by cellular guanylate kinase several other cellular kinases can add the third phosphate. The triphosphate is a more potent inhibitor of the viral DNA polymerases than of cellular DNA polymerases and also inactivates the former but not the latter. The net result is that ACV has been an effective treatment of, and prophylaxis for, genital herpes. Also it can result in dramatic relief of pain associated with shingles caused by reactivation of latent varicella-zoster virus, and has been successful in many patients with herpes encephalitis. 

Puhlmann M, Brown CK, Gnant M, Huang J, et al. 2000. Vaccinia as a vector for tumor directed gene therapy Biodistribution of a thymidine kinase-deleted mutant. Cancer Gene Ther. 7 66-73. 

BrdU 5-Bromodeoxyuridine (also abbreviated BUdR or BrdUrd) is a thymidine analog that will be incorporated into the DNA of cycling cells. Cells pulsed with BrdU can then be stained with anti-BrdU monoclonal antibodies to indicate which cells have been synthesizing DNA during the pulse period. BrdU staining is a more precise way to look at the proportion of cells in S phase than simple propidium iodide staining for DNA content. 

Condensation of LXVIa (R = p-toluyl) with monomercurithymine (prepared from 1-acetylthymine) produces a mixture of acylated nucleoside anomers (LXVlb and LXVIc, R = thyminyl) which are separated and de-esterified to thymidine and a-thymidine. Similarly, reaction of N-acetylcytosinemercury (LV) with LXVIa (R = p-chlorobenzoyl) yields the a and ft anomers of acylated 2-deoxycytidine which, after separation and deacylation, are converted smoothly to 2-deoxycytidine (LXVlb, R = H, R = cytosinyl) and its a anomer (LXVIc). In like manner, 2-deoxy-5 -fluoro-uridine and -cytidine were synthesized, along with their... 

Thirty 5 -thiourea-substituted a-thymidine analogues used to develop receptor-independent 4D-QSARmodels ( 3 = 0.83) for thymidine monophosphate kinase inhibitors. The model was also put into the context of reported crystallographically characterized inhibitor/enzyme interactions... 

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