MECHANISM OF INHIBITION OF EUKARYOTIC PROTEIN-SYNTHESIS BY TRICHOTHECENE FUNGAL TOXINS
MECHANISM OF INHIBITION OF EUKARYOTIC PROTEIN-SYNTHESIS BY TRICHOTHECENE FUNGAL TOXINS
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DOI：
10.1073/pnas.71.1.30
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发表时间：
1974-01-01
影响因子：
11.1
通讯作者：
DAVIES, J
中科院分区：
文献类型：
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作者：
CUNDLIFFE, E;CANNON, M;DAVIES, J
12,13-环氧毛霉烯，一类倍半萜类真菌抗生素，抑制真核细胞中的蛋白质合成，但不具有共同的作用模式。木霉蛋白稳定多核糖体，阻止其被嘌呤霉素分解，也阻止嘌呤霉素从核糖体释放新生肽。雪腐镰刀菌醇、T-2毒素和维rucarin A引起H-HeLa细胞中多核糖体的快速和几乎定量的分解，这一过程被大霉素、环己亚胺或木霉素所抑制。在酵母球质体中也观察到木霉素、雪valenol和维rucarin A的类似作用。我们得出结论，在真核生物中，雪腐镰刀菌醇、T-2毒素和维rucarin A是多肽链起始的有效和高选择性抑制剂，而木霉素则抑制链的延伸和（或）终止。我们比较了各种trichocene的结构式，认为在共同的trichocene环的碳-15上取代基的存在可能是确定这类化合物的精确作用模式的重要因素。
The 12,13-epoxytrichothecenes, a group of sesquiterpenoid fungal antibiotics, inhibit protein synthesis in eukaryotic cells but do not share a common mode of action. Trichodermin stabilizes polyribosomes, prevents their disaggregation by puromycin, and also prevents the release of nascent peptides from ribosomes by puromycin. Nivalenol, T-2 toxin, and verrucarin A cause rapid and almost quantitative breakdown of polyribosomes in H-HeLa cells, a process which is inhibited by anisomycin, cycloheximide, or trichodermin. Similar effects of trichodermin, nivalenol, and verrucarin A are also observed in yeast spheroplasts. We conclude that nivalenol, T-2 toxin, and verrucarin A are potent and highly selective inhibitors of polypeptide chain initiation in eukaryotes, whereas trichodermin inhibits chain elongation and (or) termination. We have compared the structural formulae of various trichothecenes and suggest that the presence of substituents on carbon-15 of the common trichothecene ring may be important in determining the precise modes of action of this group of compounds.