Nucleotides, formation

The net reaction for sugar nucleotide formation (combining the preceding two equations) is thus... 

Mercaptopurine (6MP) and 6-thioguanine (6TG) are analogs of the purines hypoxanthine and guanine, which must be activated by nucleotide formation, according to the following scheme ... 

Dickinson, D.B., Hopper, J.E., and Davies, M.D., 1973, A study of pollen enzymes involved in sugar nucleotide formation. In Loewus, F. (ed.), Biogenesis of Plant Cell Wall Polysaccharides. Academic Press, NY, pp. 29 48. 

Shen YC, Hing CY (1995) Effect of trilinolein on cyclic nucleotide formation in human platdets relationsliip with its antiplatdet effect and nitric oxide synthesis Br J Pharmacol 116 1644-1648. 

Chloro-9-cyclopentyl-8-azapurine inhibited synthesis of DNA, RNA, and protein in E. coli. Blockage of thymine-nucleotide formation was the first effect seen. Alkylation of enzymes by the 6-chloro substituent was suggested as a mechanism. This azapurine inhibited the RNA polymerase from E. coli, but not that from M. lysodeikticus. Formyltetrahydrofolate synthetases, of both mammalian and bacterial origins, were strongly inhibited. The same azapurine, at 0.3 mM, markedly inhibited the steroid-induced synthesis of A -3-ketosteroid isomerase in Pseudomonas testoster-oni ... 

A particularly intuitive application of this concept may be the experimental anticancer drug N-(phosphonoacetyl)-L-aspartate (PALA). The first step in the de novo biosynthesis of the pyrimidine nucleotide formation in the cell involves the condensation of carbamoyl phosphate with L-aspartic acid catalyzed by the enzyme aspartate transcarbamylase (Eq. 2.14).2 One can postulate a transition state, as shown in Eq. 2.14. 

Other Applications. 1 was applied in the synthesis of some important heterocyclic compounds such as oxadiazole, triazolone, quinazoline-2,4-diones, tetrahydroisoquinoline-hydantoins, and pyrazole. The activation of phosphates to phosphorimidazolides, phosphate-phosphate coupling and nucleotide formation can also rely on... 

A useful method of introduction of protected phosphates prior to nucleotide formation is shown in Scheme 3. ... 

Studies in B. subtilis [151] and E. coli [148] have implicated a special role of the purine PRTases in the regulation of purine uptake and incorporation. The degree of uptake is proportional to the PRTase activity and appears to be obligatorily linked to nucleotide formation. The adenine enzyme has been found associated with membrane vesicles, and uptake by membrane preparations is completely correlated with enzyme activity. Inhibition of Ad-PRTase activity also inhibits purine adenine uptake, thus providing strong support that the observed inhibitory effects may serve to govern cellular uptake of the purines. Such a control would prevent a cell from being overloaded with excess nucleotides. 

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