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Structural requirements of (2'-5') oligoadenylate for protein synthesis inhibition in human fibroblasts. 总被引:1,自引:1,他引:0 下载免费PDF全文
J L Drocourt C W Dieffenbach P O Ts'o J Justesen M N Thang 《Nucleic acids research》1982,10(6):2163-2174
The structural requirements of (2'-5')-oligoadenylic acid (pppA(2'p5'A)x, X greater than or equal to 1 or (2'-5'An) for inhibition of protein synthesis in cells were examined with a modified calcium-coprecipitation technique, using a series of trinucleotide analogs (pppA2'p5'A2'p5'N, N=rC, rG, rU, T, dC, dG, dA). In this system both the degree and the duration of the inhibition of protein synthesis were dependent on the added concentration of (2'-5')A3. Of all the heterotrimers, only the deoxy A derivative was active as an inhibitor of protein synthesis, while the other members of the analog series were found to have no inhibitory effects. In competition experiments between (2'-5')A3 and the non-active analogs, three heterotrimers were shown to reduce the activity of (2'-5')A3 in protein inhibition. In contrast, the dephosphorylated (2'-5')A3 had no inhibitory effect and was not effective in blocking (2'-5')A3. These results indicate that the 5'-terminal triphosphate is important for binding of (2'-5')A3 to the site of (2'-5')An action and the adenine base at the 2'-terminus is important for activating the machinery responsible for protein synthesis inhibition in the cells, most likely the (2'-5')An-activated nuclease. 相似文献
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MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs. 总被引:23,自引:0,他引:23
J D Schuetz M C Connelly D Sun S G Paibir P M Flynn R V Srinivas A Kumar A Fridland 《Nature medicine》1999,5(9):1048-1051