Mechanisms of substrate selectivity for Bacillus anthracis thymidylate kinase was written by Carnrot, Cecilia; Wang, Liya; Topalis, Dimitri; Eriksson, Staffan. And the article was included in Protein Science on September 30,2008.Safety of 1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione The following contents are mentioned in the article:
Bacillus anthracis is well known in connection with biol. warfare. The search for new drug targets and antibiotics is highly motivated because of upcoming multiresistant strains. Thymidylate kinase is an ideal target since this enzyme is at the junction of the de novo and salvage synthesis of dTTP, an essential precursor for DNA synthesis. Here the expression and characterization of thymidylate kinase from B. anthracis (Ba-TMPK) is presented. The enzyme phosphorylated deoxythymidine-5′-monophosphate (dTMP) efficiently with Km and Vmax values of 33 μM and 48 μmol mg-1 min-1, resp. The efficiency of deoxyuridine-5′-monophosphate phosphorylation was ∼10% of that of dTMP. Several dTMP analogs were tested, and D-FMAUMP (2′-fluoroarabinosyl-5-methyldeoxyuridine-5′-monophosphate) was selectively phosphorylated with an efficiency of 172% of that of D-dTMP, but L-FMAUMP was a poor substrate as were 5-fluorodeoxyuridine-5′-monophosphate (5FdUMP) and 2′,3′-dideoxy-2′,3′-didehydrothymidine-5′-monophosphate (d4TMP). No activity could be detected with 3′-azidothymidine-5′-monophosphate (AZTMP). The corresponding nucleosides known as efficient anticancer and antiviral compounds were also tested, and D-FMAU was a strong inhibitor with an IC50 value of 10 μM, while other nucleosides-L-FMAU, dThd, 5-FdUrd, d4T, and AZT, and 2′-arabinosylthymidine-were poor inhibitors. A structure model was built for Ba-TMPK based on the Staphylococcus aureus TMPK structure. Docking with various substrates suggested mechanisms explaining the differences in substrate selectivity of the human and the bacterial TMPKs. These results may serve as a start point for development of new antibacterial agents. This study involved multiple reactions and reactants, such as 1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (cas: 69256-17-3Safety of 1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione).
1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione (cas: 69256-17-3) belongs to pyrimidine derivatives. The aromatic compound pyrimidine, and its derivatives, are ubiquitous in nature. They are found in nucleic acids, vitamins, amino acids, antibiotics, alkaloids, and a variety of toxins. A Cu-catalyzed and 4-HO-TEMPO-mediated [3 + 3] annulation of commercially available amidines with saturated ketones enables an efficient and facile synthesis of structurally important pyrimidines via a cascade reaction of oxidative dehydrogenation/annulation/oxidative aromatization.Safety of 1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
69256-17-3;1-((2R,3S,4R,5R)-3-Fluoro-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione;The future of 69256-17-3;New trend of C10H13FN2O5;function of 69256-17-3