WordNet
- an antiviral drug used to combat HIV infection (同)ddC, DDC, zalcitabine
English Journal
- In vitro mitochondrial toxicity of metacavir, a new nucleoside reverse transcriptase inhibitor for treatment of hepatitis B virus.
- Zhang P1, Zhang L, Jiang Z, Wang T, Chen H, Xiong Y, Li Z.Author information 1Jiangsu Center for New Drug Screening and National Drug Screening Laboratory, China Pharmaceutical University, Nanjing, People's Republic of China.AbstractTherapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Metacavir (PNA) is a novel synthetic nucleoside analog for oral administration with potent and specific antiviral activity against hepatitis B virus (HBV). We assessed the potential for mitochondrial toxicity of PNA in long-term cultures of HepG2 hepatoma cells by measuring mitochondrial function (through lactate secretion), levels of mitochondrial DNA (mtDNA), and the activities of respiratory-chain complexes I to IV. Exposure of HepG2 cells to PNA at concentrations up to 50 μM for 15 days resulted in no deleterious effect on cell proliferation, levels of lactate or mtDNA, or enzyme activities of respiratory-chain complexes I to IV. In contrast, dideoxycytosine at 10 μM and zidovudine at 50 μM have significant effects on cell proliferation, levels of lactate and mtDNA, and enzyme activities of respiratory-chain complexes I to IV. However, PNA at a supratherapeutic concentration of 250 μM could result in significant alterations in the levels of mtDNA and the activities of respiratory-chain complex enzymes, revealing evidence of the potential mitochondrial toxicity of PNA. In summary, these in vitro results indicate that the potential for PNA to interfere with mitochondrial functions is low.
- Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2010 Nov;54(11):4887-92. doi: 10.1128/AAC.00794-10. Epub 2010 Aug 30.
- Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Metacavir (PNA) is a novel synthetic nucleoside analog for
- PMID 20805401
- Structure-function relationships in miscoding by Sulfolobus solfataricus DNA polymerase Dpo4: guanine N2,N2-dimethyl substitution produces inactive and miscoding polymerase complexes.
- Zhang H1, Eoff RL, Kozekov ID, Rizzo CJ, Egli M, Guengerich FP.Author information 1Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA.AbstractPrevious work has shown that Y-family DNA polymerases tolerate large DNA adducts, but a substantial decrease in catalytic efficiency and fidelity occurs during bypass of N2,N2-dimethyl (Me2)-substituted guanine (N2,N2-Me2G), in contrast to a single methyl substitution. Therefore, it is unclear why the addition of two methyl groups is so disruptive. The presence of N2,N2-Me2G lowered the catalytic efficiency of the model enzyme Sulfolobus solfataricus Dpo4 16,000-fold. Dpo4 inserted dNTPs almost at random during bypass of N2,N2-Me2G, and much of the enzyme was kinetically trapped by an inactive ternary complex when N2,N2-Me2G was present, as judged by a reduced burst amplitude (5% of total enzyme) and kinetic modeling. One crystal structure of Dpo4 with a primer having a 3'-terminal dideoxycytosine (Cdd) opposite template N2,N2-Me2G in a post-insertion position showed Cdd folded back into the minor groove, as a catalytically incompetent complex. A second crystal had two unique orientations for the primer terminal Cdd as follows: (i) flipped into the minor groove and (ii) a long pairing with N2,N2-Me2G in which one hydrogen bond exists between the O-2 atom of Cdd and the N-1 atom of N2,N2-Me2G, with a second water-mediated hydrogen bond between the N-3 atom of Cdd and the O-6 atom of N2,N2-Me2G. A crystal structure of Dpo4 with dTTP opposite template N2,N2-Me2G revealed a wobble orientation. Collectively, these results explain, in a detailed manner, the basis for the reduced efficiency and fidelity of Dpo4-catalyzed bypass of N2,N2-Me2G compared with mono-substituted N2-alkyl G adducts.
- The Journal of biological chemistry.J Biol Chem.2009 Jun 26;284(26):17687-99. doi: 10.1074/jbc.M109014274.
- Previous work has shown that Y-family DNA polymerases tolerate large DNA adducts, but a substantial decrease in catalytic efficiency and fidelity occurs during bypass of N2,N2-dimethyl (Me2)-substituted guanine (N2,N2-Me2G), in contrast to a single methyl substitution. Therefore, it is unclear why t
- PMID 19542237
- Synthesis of a fluorescent 2'3'-dideoxycytosine analog, tCdd.
- Porterfield W1, Tahmassebi DC.Author information 1Department of Chemistry and Biochemistry, University of San Diego, San Diego, CA 92110, USA.AbstractThe pathway leading to the preparation of a novel tricyclic 2'3'-dideoxycytosine analog, tCdd (1) is reported. A protected 2'3'-dideoxyribose prepared from l-glutamic acid was coupled to a silylated fluorescent base to yield a mixture of the alpha- and beta-anomers of the 2'3'-dideoxyribonucleoside of 1,3-diaza-2-oxophenothiazine, tCdd (1). The fluorescent base analog retains a high fluorescence emission over a large pH range and should be useful in a variety of probe applications.
- Bioorganic & medicinal chemistry letters.Bioorg Med Chem Lett.2009 Jan 1;19(1):111-3. doi: 10.1016/j.bmcl.2008.11.015. Epub 2008 Nov 9.
- The pathway leading to the preparation of a novel tricyclic 2'3'-dideoxycytosine analog, tCdd (1) is reported. A protected 2'3'-dideoxyribose prepared from l-glutamic acid was coupled to a silylated fluorescent base to yield a mixture of the alpha- and beta-anomers of the 2'3'-dideoxyribonucleoside
- PMID 19026534
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