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Synthesis and Biological Activities of Novel s-Triazine Bridged dinucleoside Analogs

Chinese Journal of Chemistry 2011年第6期29卷 1205-1210页

作者： Shen, Fengjuan Li, Xiaoliu Zhang, Xiaoyuan Qin, Zhanbin Yin, Qingmei Chen, Hua Zhang, Jinchao Key Laboratory of Chemical Biology of Hebei Province College of Chemistry and Environmental Science Hebei University Baoding Hebei 071002 China College of Science Hebei University of Science & Technology Shijiazhuang Hebei 050018 China

A series of novel dinucleosides linked by s-triazine were synthesized via the nucleophilic substitution reaction of amino nucleoside and cyanuric chloride in THF/H20. The biological activities of these novel dinucleos... 详细信息

关键词： dinucleoside s-triazine HIV-RT inhibition cyanuric chloride

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Mathematical model for the ubiquitin activating enzyme E1

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Journal of Biomedical Science and Engineering 2010年第3期3卷 274-284页

作者： Francisco Javier López-Cánovas Francisca Cánovas María Antonia Günther Sillero Antonio Sillero 不详

The ubiquitin-activating enzyme E1 (EC 6.***.2.19) represents the first step in the degradation of proteins by the ubiquitin proteasome pathway. E1 transfers ubiquitin from the ubiquitinated E1 to the ubiquitin carrier proteins (E2), ubiquitin-protein ligases (E3) and proteins. This process is rather complex, and known from the work of Haas, Ciechanover, Hershko, Rose and others. The occurrence of 19 hypothetical intermediate enzyme forms (EFs) and 22 different reactions were considered in the presence of ubiquitin (Ub), ATP, adenosine 5’-tetraphosphate (p4A), pyrophosphate (P2), and tripolyphosphate (P3) as substrates, and iodoacetamide (IAA) and dithioth- reitol (DTT) as inhibitors. Inspired by the work of Cha (Cha (1968) J. Biol. Chem., 243, 820-825) we have treated these reactions in two complementary ways: in rapid equilibrium and in steady state. The kinetics of both types of reactions were simulated and solved with a system of ordinary differential equations using the Mathematica Program. The ubiquitination of E1 has been also theoretically coupled to the ubiquitination of E2, E3 and proteins. This makes the model useful to predict the theoretical influence of inhibitors (or of changes in some parameters of the reaction) on the ubiquitination of proteins. The Program responds to changes in the concentration of ATP or ubiquitin and has predictive properties as shown by the influence of AMP on the synthesis of p4A, calculated theoretically and confirmed experimentally.

关键词： dinucleoside Polyphosphates Adenosine Tetraphosphate Tripolyphosphate Proteasome Mathematical Model

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