Cytidine 5-methyl-2 -deoxycytidine

The similarity in the pyrimidine carbon resonances in cytidine and deoxycytidine is indicative of the independence of these shifts from the sugar fragments. The differences observed between the chemical shifts of uracil and thymine, or uridine and thymidine, indicate that they must result from the presence of the 5-methyl group in the latter. The downfield shifts ( — 7.5 ppm) of the 05 peaks of uracil or uridine upon 5-methyl substitution are typical for a carbon directly substituted by a... 

Downfield chemical shift changes are given as negative numbers and are in cycles per second. In all cases except cytidine and 5 -methyl-2 -deoxycytidine, inhibitor concentrations were sufficient to saturate the enzyme between pH 5 and 7. [Reproduced from Meadows et al. (465).]... 

Figure 4 Catalytic activation of cytosine for C5-methylation by nucleophilic addition of a thiolate at the C6 position, (a) The chemical mechanism of enzymatic DNA cytosine-S methylation. Mechanism-based inhibition of DMA MTases by cytidine analogs 5-fluoro-2 -deoxycytidine (b), 5-aza-2 -deoxy-cytidine (c), and 2-pyrimidinone-l-p-D-(2 -deoxyriboside) (d).

The synthesis of deoxyuridine, cytidine, deoxycytidine and thymidine nucleotides from UMP (Fig. 6.13) involves three reactions CTP synthetase, ribonucleotide reductase, and thymidylate synthase (80). The first enzyme converts UTP into CTP and the second catalyzes the conversion of CDP, UDP, ADP and GDP into their respective deoxyribonucleotides. The last enzyme, thymidylate synthase, catalyzes the reductive methylation of deoxyUMP at the C-5 position giving deoxyTMP. The human enzyme has been extensively studied as it is a target enzyme in cancer chemotherapy. Besides these three enzymes, two other enzymes are involved in pyrimidine nucleotide synthesis and interconversion. DeoxyCMP deaminase converts deoxyCMP into deoxyUMP and deoxyUTP triphosphatase converts deoxyUTP into deoxyUMP. Giardia lamblia, and Trichomonas vaginalis lack both ribonucleotide reductase and thymidylate synthase and... 

The photoinduced intramolecular electron transfer reactions of some poly-(ethylene glycol)-linked 9-aminoacridine-benzoate electron donor-acceptor systems have been described. Photosensitized oxidation of 5-methyl-2 -deoxy-cytidine using menadione (2-methylnaphthalene-l,4-dione) gives 5,6-dihydroxy-5,6-dihydro-5-methyl-2 -deoxycytidine in what is thought to be an electron... 

Metabolism of the pyrimidine deoxyribonucleotides is more complex because, in addition to transfer of phosphoryl groups, deamination and methylation reactions occur at this level. Specifically, the thymidine phosphates are derived by methylation of deoxyuridylate, and the latter may be derived from the deoxycytidine phosphates by way of deoxycytidylate deaminase. The deoxycytidine phosphates are not formed by amination of deoxyuridine phosphates, but are derived entirely from the cytidine phosphates by enzymatic reduction (Chapter 16). 

Deoxycytidylate deaminase was first isolated from sea urchin e s by Scarano and has since been demonstrated in many animal tissues the deaminases from spleen and chick embryo have been partly purified (23, 24). The enzyme requires that the substrate must be a 4-aminopyrimidine deoxyribonucleoside 5 -monophosphate, and will accept the following substituents at the pyrimidine 5-position methyl, hydroxymethyl, fluoro, iodo, and bromo. Notably, the following are not deaminated cytidine, deoxycytidine, eytidylate, dCDP, and dCTP. The concentration of this enzyme in cells appears to be related to their proliferative state in that the enzyme is found in growing tissues, but activities are low in adult tissues such as liver. 

There have been many reports of syntheses of deoxy nucleosides by standard sugar-base condensation reactions. These include 5 -deoxy-ribo nucleosides and 5 -mono- or 5",5-di-deuterated analogues, as well as derivatives of 5-deoxy-D-xylose and 5-deoxy-D-glucose, 5-alkylated thymidine derivatives, 2 -deoxy-6-methyl-5-azacytidine and its a-anomer, the thymidine analogue 4-(2-deoxy-B-D-erythro-pento-furanosyl)-6-methyl-l,2,4-triazine 3(HH)-one-1-oxide, 6-aza-3-deaza analogues of 2 -deoxy-cytidine and 2 -deoxyuridine,3 -deoxycytidine from a 3-deoxy-ribofuranose obtained from a fermentation broth producing the 3 -deoxy nucleoside antibiotic, cordycepin, 4-deoxy-DL-threo-pentopyranosyl pyrimidine nucleosides, and 5 -C-methyluridines derived from 6-deoxy-D-allose and 6-deoxy-D-talose. A range... 

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