中文摘要：脱氧雪腐镰刀菌烯醇是单端孢霉烯族的一种食源性真菌毒素，可能给人体和动物造成严重损伤。单端孢霉烯族通过与核糖体的相互作用来抑制蛋白质合成是一种已知的毒性作用的关键机制。然而，尚未完全了解单端孢霉烯族化合物如何以及在何种程度上影响人体和动物的健康。相应地，这种情况导致管理相关健康风险的延迟。针对支持危害识别的过程，生物信息学分析会成为研究单端孢霉烯族毒素的结构-活性关系，找出在风险评估过程中可能关注的分子的简单工具。在此框架下，本研究通过分子建模法，在构效关系视角下研究了单端孢霉烯族毒素与核糖体相互作用的结构基础。
外文摘要：Deoxynivalenol is a foodborne mycotoxin belonging to the trichothecenes family that may cause severe injuries in human and animals. The inhibition of protein synthesis via the interaction with the ribosome has been identified as a crucial mechanism underlying toxic action. However, it is not still fully understood how and to what extent compounds belonging to trichothecenes family affect human and animal health. In turn, this scenario causes delay in managing the related health risk. Aimed at supporting the hazard identification process, the in silico analysis may be a straightforward tool to investigate the structure-activity relationship of trichothecenes, finding out molecules of possible concern to carry forth in the risk assessment process. In this framework, this work investigated through a molecular modeling approach the structural basis underlying the interaction with the ribosome under a structure-activity relationship perspective. To identify further forms possibly involved in the total trichothecenes-dependent ribotoxic load, the model was challenged with a set of 16 trichothecene modified forms found in plants, fungi and animals, including also compounds never tested before for the capability to bind and inhibit the ribosome. Among them, only the regiospecific glycosylation in the position 3 of the sesquiterpenoid scaffold (i.e. T-2 toxin-3-glucuronide, α and β isomers of T-2 toxin-3-glucoside and deoxynivalenol-3-glucuronide) was found impairing the interaction with the ribosome, while the other compounds tested (i.e. neosolaniol, nivalenol, fusarenon-X, diacetoxyscirpenol, NT-1 toxin, HT-2 toxin, 19- and 20-hydroxy-T-2 toxin, T-2 toxin triol and tetraol, and 15-deacetyl-T-2 toxin), were found potentially able to inhibit the ribosome. Accordingly, they should be included with high priority in further risk assessment studies in order to better characterize the trichothecenes-related hazard.
外文关键词：Trichothecenes；Deoxynivalenol；Ribotoxicity；Toxicodynamic；Modified mycotoxins；in silico toxicology；Toxicity
作者：Dellafiora, L；Galaverna, G；Dall'Asta, C
作者单位：Univ Parma
期刊名称：TOXICOLOGY LETTERS
期刊影响因子：3.522
出版年份：2017
出版刊次：3
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