Thymidine 5’-diphosphate

Figure 12-29 Drawing showing the hydrogen-bonding interactions between the guanidinium ions of arginines 35 and 87 of the micrococcal (staphylococcal) nuclease with the 5 -phosphate of the inhibitor thymidine 3, 5 -diphosphate in the complex of E + I + Ca2+. A possible mechanism is illustrated. A hydroxyl ion bound to Ca2+ carries out an in-line attack on the phosphorus. See Libson et al.S26...

Fig. 12. Active site of wild-type staphylococcal nuclease with bound active site ligands Ca and thymidine 3, 5 -diphosphate. Reproduced with permission from Ref. 88.

Thymidine cyclic 3, 5 -(methylphosphate), C-165 Thymidine diphosphate, T-105 Thymidine 3, 5 -diphosphate, T-106 Thymidine 3 -phosphaie, T-107 Thymidine 5 -phosphate, T-108... 

Cotton et al. report the high-resolution structure of an inhibitor complex of the extracellular nuclease of Staphylococcus aureus. The 2 A resolution electron-density map was based on the analysis of two heavy-atom derivatives one involves the replacement of the calcium ion for a barium, while the other uses 5-iododeoxyuridine 3, S -diphosphate in place of thymidine 3 5 -diphosphate, a replac rait of Me by 1. 

It has been shown that purine-pyrimidine dinucleotides are considerably more add-labile than pyrimidine-pyrimidine dinudeotides and that the cytosine deox3uibose bond is more labile than the thymine deoxyribose bond. Thus, when thymidylic-uridylic add dinucleotide is hydrolyzed more thymidine 3, 5 -diphosphate is formed lhan uridine 3, 5 -diphos-phate [Eq. 56]. On the basis of these data an attempt was made to gain information on the distribution of pyrimidine deoxynucleotides in different preparations of DNA (255). Differences were detected in the rate of appearance of the pyrimidine deoxynucleoside dipho hates, i.e., early appearance from isolated pyrimidine deoxynucleotides and later appearance from adjoining pjuimidine deoxynucleotide sequences. This indicates that the distribution of pyrimidines in DNA is not random and differs from one preparation to another, even in samples of DNA with the same base composition. 

Figure 20-7. Summary of the interrelationships in metabolism of amino sugars. (At asterisk Analogous to UDPGIc.) Other purine or pyrimidine nucleotides may be similarly linked to sugars or amino sugars. Examples are thymidine diphosphate (TDP)-glucosamine and TDP-N-acetylglucosamine.

A mutant strain of Escherichia coli Y-10, defective in L-rhamnose synthesis, accumulates109 a considerable amount of thymidine diphosphate sugars. Three of them were identified110 as the esters of thymidine 5 -pyrophosphate with 6-deoxy-a-D-xyZo-hexopyranos-4-ulose (28), 6-deoxy-D-glucose, and D-fucose. The fourth component was found to be a 4-acetamido-4,6-dideoxy-D-galactose derivative111,112 (29) it occurs also in Pasteurella pseudotuberculosis102 and its... 

O. Gabriel and G. Ashwell, Biological mechanisms involved in the formation of deoxysugars. I. Preparation of thymidine diphosphate glucose labelled specifically in carbon 3, J. Biol. Chem., 240 (1965) 4123-4127. 

Nakano, Y., Suzuki, N., Yoshida, Y., Nezu, T., Yamashita, Y., Koga, T. Thymidine diphosphate-6-deoxy-l-lyxo-4-hexulose reductase synthesizing dTDP-6-deoxy-l-talose from Actinobacillus actinomycetemcomitans. J Biol Chem 275 (2000) 6806-6812. 

Thymine Deoxyribose Thymidine Thymidylic acid thymidine monophosphate (dTMP) Thymidine diphosphate (dTDP) Thymidine triphosphate (dTTP)... 

Borch reported the synthesis of thymidine diphosphate glucose (107) via a new method that employs a highly reactive zwitterionic phosphoramidate intermediate as the phosphorylating species (Scheme 2). This methodology was also used... 

In order to develop a purification procedure of thymidine 5 -diphosphate-glucose-4,6-dehydratase based on affinity chromatography, novel activated thymidine diphosphate analogues that display high affinity for the dehydratase have been synthesised. These diphosphate analogues have been derived from... 

The methyl group attached to the 5-OH arises by transfer of the methyl of S-adenosylmethionine catalyzed by a specific 0-methyltransferase [21]. A specific 5-ketoreductase has been shown to convert 5-keto avermectins into the B components [22]. The glycosyltransferase which catalyzes the stepwise transfer of oleandrose from thymidine diphosphate oleandrose to the aglycone has been demonstrated in cell free extracts [23]. Whether the sugars are transferred sequentially is not clear. 

C. Thymidine diphosphate-X dTDP-hexoses D-glucose, D-mannose,... 

A number of conjugated deoxyribonucleoside diphosphates are known, although those knoum are less numerous than similar compounds of the ribose series. For example, dCDP-choline and dCDP-ethanolamine have been found in sea urchin eggs and in animal tissues, but their significance is unknown. Various thymidine diphosphate sugars (see Table l-I) have been isolated from bacterial cells these compounds ser e as coenzymes in the synthesis of polysaccharides in Salmonella typhimurium. 

Marumo K, Lindquist L. Verma N. Weintraub A, Reeves P, Lindbetg AA. Enzymatic synthesis and isolation of thymidine dipho phate-6-slcoxY D Xy(o-4 hexulose and thymidine diphosphate-L-ihamnose. Eur J Biochem 1992 204 539-545. 

Matsuhashy M, Strominger JL. Thymidine diphosphate 4-acetamido 4,6 dideoxyhcxoses. 1. Enzymatic synthesis by straiits of Eschencfiiaeob. J Biol Chem 1966 239 2454-2463. 

Leloir-GTs utilize sugar nucleotides as activated donor substrates. Sugar moieties bound to nucleoside mono- or diphosphates, like cytosine monophosphate (CMP), thymidine diphosphate (dTDP), guanosine diphosphate (GDP), and the most common uridine diphosphate (UDP), are transferred by two types of Leloir-GTs. 

D., Uou, K.-K., Lee, H.-C., Sohng, J.-K. et al. (2010) One-pot enzymatic synthesis of deoxy-thymidine-diphosphate (TDP)-2-deoxy-a-d-glucose using phos-phomannomutase. J. Mol. Catal. E ... 

The a,p-imido analogue (116) of thymidine diphosphate has been prepared i 9 and 5 -0-(a-thio)tilphosphates of some 2, 3 -dideojgmucleosides have been synthesized. A cyclic dimer of FDU monophosphate has been shown to have in vivo antitumour activity as does FDU itself, and with less toxicity. 

Fig. 14. Effect of 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine (5-FdUMP) on the synthesis of RNA and DNA. 5-FU is incorporated into RNA whereas 5-FdUMP inhibits thymidilate synthetase competitively and blocks DNA synthesis. The conversion of thymidine (dTr) into thymidilate (dTMP) by means of thymidine kinase is only a subsidary routine to thymidilate which can become important, however, under certain conditions such as in developing pollen (page 185). U = uridine triphosphate, Tr = thymidine, TMP = thymidine monophosphate = thymidilate, TDP = thymidine diphosphate, TTP = thymidine triphosphate, 5-F = 5-fluoro, d = deoxy, 1 = thymidine kinase, 2 = thymidilate synthetase.

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