Adenosine methylation

Nucleotide derivatives. Dry adenosine-5 -phosphoric acid stirred with -carb-ethoxy-a-ethoxyvinyl diethyl phosphate and tri-n-butylamine in abs. dimethyl-formamide until dissolved after 2-3 days, dil. with acetone and the product precipitated with a soln. of anhydrous Nal in acetone Na P -(5 -adenosyl) P -diethyl diphosphate (Y 87 % as the monohydrate) warmed 3 hrs. at 50° in abs. methanol-pyridine, and the product isolated as the NH4-salt NH4 5 -adenosine methyl phosphate (Y 79.2% as the monohydrate).—Pyrophosphoric acid esters react with alcohols, amines, and acids so that the monoester part appears in the product. The adenosine-5 -phosphoric acid group in the intermediate triester is activated and can be easily combined with various nucleophiles. F. e. without isolation of the intermediate s. F. Cramer and R. Witt-mann. B. 9A, 328 (1961) s. a. B. 94, 322 dimethylformamide as phosphorylation catalyst s. B, 94, 989. 

The antiviral activity of (5)-DHPA in vivo was assessed in mice inoculated intranasaHy with vesicular stomatitis vims ( 5)-DHPA significantly increased survival from the infection. (5)-DHPA did not significantly reduce DNA, RNA, or protein synthesis and is not a substrate for adenosine deaminase of either bacterial or mammalian origin. However, (5)-DHPA strongly inhibits deamination of adenosine and ara-A by adenosine deaminase. Its mode of action may be inhibition of Vadenosyl-L-homocysteine hydrolase (61). Inhibition of SAH hydrolase results in the accumulation of SAH, which is a product inhibitor of Vadenosylmethionine-dependent methylation reactions. Such methylations are required for the maturation of vital mRNA, and hence inhibitors of SAH hydrolase may be expected to block vims repHcation by interference with viral mRNA methylation. 

Adenosine, N -dimethyI-5 -0-methyI-2, 3 -0-isopropylidene-methylation, 5, 537 Adenosine, homocitrullyamino-biological activity, 5, 603 Adenosine, 1-isopentenyI-synthesis, 5, 594 Adenosine, 2 -0-methyI-occurrence, 5, 600 Adenosine, 2-phenyIamino-synthesis, 5, 590 Adenosine, 2, 3, 5 -tri-0-acetyl bromination, 5, 540 Adenosine-8-earboxylic acids synthesis, 5, 593 Adenosines, isopropylidene-synthesis, 5, 584... 

Thiamine can be considered to be the product of the quatemization of 4-methyl-5-(2-hydroxymethyl)thiazole (5) by an active derivative of 4-amino-5-(hydroxymethyl)-2-methyl pyrimidine (4) (Scheme 2). In living cells, pyramine can be activated by conversion into the diphosphate 7, via monophosphate 6, and the substrate of the enzyme responsible for the quatemization is not the thiamine thiazole, but its phosphate 8. The product of the condensation, thiamine phosphate (9), is finally converted into diphosphate 2—the biochemically active derivative—by hydrolysis to free thiamine, followed by diphosphorylation, or more directly, in some cases. Enzymes are known for all of the steps depicted in Scheme 2, and adenosine triphosphate (ATP) is, as usual, the phosphate donor. 

Basha PM, Nayeemunnisa. 1993a. Effect of methyl parathion on Na, K, and Mg adenosine triphosphatase activity in developing central nervous system in rats. Indian J Exp Biol 31 785-787. 

NM283 S282T 21 2 C-Methyl-Adenosine Reduces binding with inhibitor (Dutartre et al. 2006)... 

Catalysis by flavoenzymes has been reviewed and various analogues of FAD have been prepared e.g. P -adenosine-P -riboflavin triphosphate and flavin-nicotinamide dinucleotide ) which show little enzymic activity. The kinetic constants of the interaction between nicotinamide-4-methyl-5-acetylimidazole dinucleotide (39) and lactic dehydrogenase suggest the presence of an anionic group near the adenine residue at the coenzyme binding site of the enzyme. ... 

ROP Retinopathy of prematurity ROS Reactive oxygen species R-PIA R-(l-methyl-I-phenyltheyl)-adenosine RPMI 1640 Roswell Park Memorial Institute 1640 medium RS Reiter s syndrome RSV Rous sarcoma virus RTE Rabbit tubular epithelium RTE-a-5 Rat tubular epithelium ant n a-5... 

The analogons deamination reaction is not observed in l-methyl-2 -deoxy-adenosine nncleosides. ° Rather, in the adenine series, the Dimroth rearrangement occnrs (Scheme 8.4). On the contrary, in styrene adducts of 2 -deoxyadenosine, the hydroxyl residue of the adduct undergoes intramolecular reaction with the base to initiate deamination (Scheme 8.6). ° ° Similarly, cytosine residues bearing styrene adducts at the N3-position undergo rapid deamination (nearly complete deamination is seen within 75h). °°... 

Figure 12 Gradient separation of bases, nucleosides and nucleoside mono- and polyphosphates. Column 0.6 x 45 cm. Aminex A-14 (20 3 p) in the chloride form. Eluent 0.1 M 2-methyl-2-amino-l-propanol delivered in a gradient from pH 9.9-100 mM NaCl to pH 10.0-400 mM NaCl. Flow rate 100 ml/hr. Temperature 55°C. Detection UV at 254 nm. Abbreviations (Cyt) cytosine, (Cyd) cytidine, (Ado) adenosine, (Urd) uridine, (Thyd) thymidine, (Ura) uracil, (CMP) cytidine monophosphate, (Gua) guanine, (Guo) guanosine, (Xan) xanthine, (Hyp) hypoxanthine, (Ino) inosine, (Ade) adenosine, (UMP) uridine monophosphate, (CDP) cytidine diphosphate, (AMP) adenosine monophosphate, (GMP) guanosine monophosphate, (IMP) inosine monophosphate, (CTP) cytidine triphosphate, (ADP) adenosine diphosphate, (UDP) uridine monophosphate, (GDP) guanosine diphosphate, (UTP) uridine triphosphate, (ATP) adenosine triphosphate, (GTP), guanosine triphosphate. (Reproduced with permission of Elsevier Science from Floridi, A., Palmerini, C. A., and Fini, C., /. Chromatogr., 138, 203, 1977.)...

Ci0HuN5O10P2- C4H12N03+ 2 H20 Adenosine 5 -[tris(hydroxy-methyl)methylammonium diphosphate], dihydrate (HMADPH)203 P2i Z = 2 Dx = 1.65 R = 0.047 for 1,624 reflections. The disposition of the base is anti (75.5°). The D-ribosyl group is T (183.0°, 35.4°) and the orientation about the exocyclic, C-4 - C-5 bond is gauche + (53.7 °). These features are similar to those of the favored conformations adopted by the nucleotide monophosphates. The pyrophosphate chain displays... 

Figure 6 Structure of PD81,723, (2-amino-4,5-dimethyl-trienyl)[3-(trifluoro-methyl) phenyl]methanone and adenosine At agonists/antagonists.

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