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Pyrimidine Nucleosides (pyrimidine + nucleoside)
Selected AbstractsMicrowave-Enhanced Sonogashira Coupling Reaction of Substituted Pyrimidinones and Pyrimidine Nucleosides.CHEMINFORM, Issue 13 2004Elena Petricci Abstract For Abstract see ChemInform Abstract in Full Text. [source] Microwave-Assisted C-5 Iodination of Substituted Pyrimidinones and Pyrimidine Nucleosides.CHEMINFORM, Issue 41 2003Lisa Paolini Abstract For Abstract see ChemInform Abstract in Full Text. [source] Synthesis and Characterization of Oligodeoxynucleotides Containing Naphthyridine:Imidazopyridopyrimidine Base Pairs at their Sticky Ends.CHEMBIOCHEM, Issue 12 2006Application as Thermally Stabilized Decoy Molecules Abstract We describe the synthesis and properties of oligodeoxynucleotides (ODNs) containing 1,8-naphthyridine C-nucleoside (Na-NO) and imidazo[5,,4,:4,5]pyrido[2,3- d]pyrimidine nucleoside (Im-ON) at the termini. The modified ODNs were more resistant (6 to 40 times) than natural DNA to snake venom phosphodiesterase (SVPD). Although incorporation of one pair each of Na-NO:Im-ON on the sticky ends of the duplex was insufficient for thermal stabilization (+2.5,°C per pair relative to the G:C pair), the duplex containing two consecutive Na-NO:Im-ON pairs at its sticky ends was markedly stabilized thermally. The stabilizing effect of the incorporation of additional Na-NO:Im-ON pairs is estimated to be +7.8,°C per pair. Application as thermally stabilized decoy molecules to NF-,B (p50) was also demonstrated. The DNA duplexes containing the Na-NO:Im-ON pairs (ODN,I:ODN,II and ODN,III:ODN,IV) acted as competitors to the natural NF-,B-binding duplex (ODN,V: ODN,VI), and the calculated IC50 values of ODN,I:ODN,II and ODN,III:ODN,IV were 20.1±13.3 and 10.9±4.8 nM, respectively, greater than that of ODN,V:ODN,VI. [source] Nucleoside transporter expression and function in cultured mouse astrocytesGLIA, Issue 1 2005Liang Peng Abstract Uptake of purine and pyrimidine nucleosides in astrocytes is important for several reasons: (1) uptake of nucleosides contributes to nucleic acid synthesis; (2) astrocytes synthesize AMP, ADP, and ATP from adenosine and GTP from guanosine; and (3) adenosine and guanosine function as neuromodulators, whose effects are partly terminated by cellular uptake. It has previously been shown that adenosine is rapidly accumulated by active uptake in astrocytes (Hertz and Matz, Neurochem Res 14:755,760, 1989), but the ratio between active uptake and metabolism-driven uptake of adenosine is unknown, as are uptake characteristics for guanosine. The present study therefore aims at providing detailed information of nucleoside transport and transporters in primary cultures of mouse astrocytes. Reverse transcription-polymerase chain reaction identified the two equilibrative nucleoside transporters, ENT1 and ENT2, together with the concentrative nucleoside transporter CNT2, whereas CNT3 was absent, and CNT1 expression could not be investigated. Uptake studies of tritiated thymidine, formycin B, guanosine, and adenosine (3-s uptakes at 1,4°C to study diffusional uptake and 1,60-min uptakes at 37°C to study concentrative uptake) demonstrated a fast diffusional uptake of all four nucleosides, a small, Na+ -independent and probably metabolism-driven uptake of thymidine (consistent with DNA synthesis), larger metabolism-driven uptakes of guanosine (consistent with synthesis of DNA, RNA, and GTP) and especially of adenosine (consistent with rapid nucleotide synthesis), and Na+ -dependent uptakes of adenosine (consistent with its concentrative uptake) and guanosine, rendering neuromodulator uptake independent of nucleoside metabolism. Astrocytes are accordingly well suited for both intense nucleoside metabolism and metabolism-independent uptake to terminate neuromodulator effects of adenosine and guanosine. © 2005 Wiley-Liss, Inc. [source] The structure of human deoxycytidine kinase in complex with clofarabine reveals key interactions for prodrug activationACTA CRYSTALLOGRAPHICA SECTION D, Issue 2 2006Yan Zhang Clofarabine [2-chloro-9-(2-deoxy-2-fluoro-,- d -arabinofuranosyl)-9H -purin-6-amine] is a hybrid of the widely used anticancer drugs cladribine and fludarabine. It is the precursor of an effective chemotherapeutic agent for leukemias and other hematological malignancies and received accelerated approval by the FDA for the treatment of pediatric patients with relapsed or refractory acute lymphoblastic leukemia. Clofarabine is phosphorylated intracellularly by human deoxycytidine kinase (dCK) to the 5,-monophosphate, which is the rate-limiting step in activation of the prodrug. dCK has a broad substrate specificity, with a much higher activity to deoxycytidine than to deoxyadenosine and deoxyguanosine. As a purine-nucleoside analog, clofarabine is a better substrate of dCK than deoxycytidine. The crystal structure of dCK has been solved previously in complex with pyrimidine nucleosides and ADP [Sabini et al. (2003), Nature Struct. Biol.10, 513,519]. In the current study, the crystal structure of clofarabine- and ADP-bound dCK was solved to 2.55,Å by molecular replacement. It appears that the enzyme takes the same conformation as in the structures of the pyrimidine nucleoside-bound complexes. The interactions between 2-Cl and its surrounding hydrophobic residues contribute to the high catalytic efficiency of dCK for clofarabine. [source] Reactions of {4-[Bis(2-chloroethyl)amino]phenyl}acetic Acid (Phenylacetic Acid Mustard) with 2,-DeoxyribonucleosidesCHEMISTRY & BIODIVERSITY, Issue 3 2007Diana Florea-Wang Abstract Phenylacetic acid mustard (PAM; 2), a major metabolite of the anticancer agent chlorambucil (CLB; 1), was allowed to react with 2,-deoxyadenosine (dA), 2,-deoxyguanosine (dG), 2,-deoxycytidine (dC), 2,-deoxy-5-methylcytidine (dMeC), and thymidine (T) at physiological pH (cacodylic acid, 50% base). The reactions were followed by HPLC and analyzed by HPLC/MS and/or 1H-NMR techniques. Although the predominant reaction observed was hydrolysis of PAM, 2 also reacted with various heteroatoms of the nucleosides to give a series of products: compounds 5,31. PAM (2) was found to be hydrolytically slightly more stable than CLB (1). The principal reaction sites of 2 with dA, dG, and with all pyrimidine nucleosides were N(1), N(7), and N(3), resp. Also, several other adducts were detected and characterized. There was no significant difference in the reactivity of 1 and 2 with dG, dA or T, but the N(3) dC,PAM adduct was deaminated easier than the corresponding CLB derivative. The role of PAM,2,-deoxyribonucleoside adducts on the cytotoxic and mutagenic properties of CLB (1) is discussed. [source] Pyrimidine as Constituent of Natural Biologically Active CompoundsCHEMISTRY & BIODIVERSITY, Issue 1 2005Irene This review describes the various manifestations of the pyrimidine system (alkylated, glycosylated, benzo-annelated.). These comprise pyrimidine nucleosides as well as alkaloids and antibiotics , some of them have been discovered and isolated from natural sources already long time ago, others have been reported very recently. A short overview on pyrimidine syntheses (prebiotic synthesis, biosynthesis, and metabolism) is given. The biological activities of most of the pyrimidine analogs are briefly described, and, in some cases, syntheses are formulated. [source] Highly Concise Synthesis of 3'-"Up"-ethynyl-5'-methylbicyclo- [3.1.0]hexyl Purine and Pyrimidine Nucleoside Derivatives Using Rhodium(II) Carbenoid Cycloaddition and Highly Diastereoselective Grignard ReactionCHINESE JOURNAL OF CHEMISTRY, Issue 12 2009Zunhua Yang Abstract Synthesis of north -5'-methylbicyclo[3.1.0]hexyl purine and pyrimidine nucleosides with an ethynyl group at C-3' position has been successfully accomplished by a facile method. Methylbicyclo[3.1.0]hexanone (±)- 5 having three contiguous chiral centers was remarkably simply constructed only by four steps containing a carbenoid insertion reaction in the presence of rhodium(II) acetate dimer and CuSO4, giving a correct relative stereochemistry of the generated three chiral centers. Upon Grignard reaction of (±)- 5 with ethynylmagnesium bromide, exclusive diastereoselectivity was observed. Condensation of glycosyl donor (±)- 9 with purine nucleobase afforded only the desired N9 -alkylated nucleoside, while condensation with pyrimidine, N3 -benzoylated uracil gave the desired N1 -alkylated nucleoside (±)- 13 with the undesired O2 -alkylated nucleoside (±)- 14. Probably, (±)- 14 would be formed due to steric hindrance caused upon approaching for N1 -alkylation. [source] | ||||||||||