INHIBITION OF TRANSLATION IN EUKARYOTIC SYSTEMS BY HARRINGTONINE
INHIBITION OF TRANSLATION IN EUKARYOTIC SYSTEMS BY HARRINGTONINE
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DOI：
10.1111/j.1432-1033.1977.tb11256.x
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发表时间：
1977-01-01
期刊：
影响因子：
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通讯作者：
VAZQUEZ, D
中科院分区：
文献类型：
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作者：
FRESNO, M;JIMENEZ, A;VAZQUEZ, D
三尖杉属生物碱三尖杉酯碱、高三尖杉酯碱和异三尖杉酯碱抑制真核[兔子和酵母]细胞中的蛋白质合成。在模型系统中，[抗肿瘤]生物碱不会抑制起始过程的任何步骤，但会阻断多聚（U）定向的聚苯丙氨酸合成以及片段反应测定中肽键的形成，稀疏霉素诱导的（C）U-A-C-C-A-[3H]Leu-Ac的结合以及Phe-tRNA的酶和非酶结合 核糖体。这些结果表明三尖杉生物碱通过阻止底物与 60-S 核糖体亚基上的受体位点结合并阻断氨酰基-tRNA 结合和肽键形成来抑制翻译延伸期。三尖杉生物碱不抑制多核糖体中的多肽合成和肽基-[3H]嘌呤霉素形成。这些生物碱抑制[14C]木霉菌素与游离核糖体的结合，但几乎不影响抗生素与酵母多聚体的相互作用。这些结果表明三尖杉生物碱不能与多核糖体相互作用，仅抑制伸长的初始周期。这解释了一些工人在三尖杉酯碱存在下观察到的多核糖体流失。
The Cephalotaxus alkaloids harringtonine, homoharringtonine and isoharringtonine inhibit protein synthesis in eukaryotic [rabbit and yeast] cells. The [antitumor] alkaloids do not inhibit, in model systems, any of the steps of the initiation process but block poly(U)-directed polyphenylalanine synthesis as well as peptide bond formation in the fragment reaction assay, sparsomycin induced binding of (C)U-A-C-C-A-[3H]Leu-Ac and enzymic and the nonenzymic binding of Phe-tRNA to ribosomes. These results suggest that the Cephalotaxus alkaloids inhibit the elongation phase of translation by preventing substrate binding to the acceptor site on the 60-S ribosome subunit and block aminoacyl-tRNA binding and peptide bond formation. The Cephalotaxus alkaloids do not inhibit polypeptide synthesis and peptidyl-[3H]puromycin formation in polysomes. These alkaloids inhibit [14C]trichodermin binding to free ribosomes but hardly affect the interaction of the antibiotic with yeast polysomes. These results suggest that the Cephalotaxus alkaloids cannot interact with polysomes and only inhibit the initial cycles of elongation. This explains the polysome run off observed by some workers in the presence of harringtonine.